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[[File:Mantzoros.tif|thumb|Christos Socrates Mantzoros]]
[[File:Mantzoros.tif|thumb|Christos Socrates Mantzoros]]
'''Christos Socrates Mantzoros''' is a Greek American physician scientist, internist - endocrinologist, researcher, [[Harvard Medical School]] professor and the editor-in-chief of the journal [[Metabolism: Clinical and Experimental]]. He is considered a pioneer and worldwide expert in obesity and metabolism. He has given more than 500 lectures nationally and internationally on these critical topics. His research has resulted in more than 600 publications in Medline, more than 145 publications under the collaborative Look Ahead Research Group, more than 170 chapters and reviews and has received more than 50,000 citations (Google Scholar) as well as prestigious awards at national and international meetings.<ref>{{cite web|url=https://www.ncbi.nlm.nih.gov/pubmed/?term=Mantzoros+C%5BAuthor%5D|title= Christos Mantzoros' Publications on PubMed - PubMed - NCBI|first=|last=pubmeddev|publisher=}}</ref> He has an H index of 114.<ref>{{cite web|url=https://scholar.google.com/citations?user=PllPdaAAAAAJ&hl|title=Christos Mantzoros - Google Scholar Citations|publisher=}}</ref>
'''Christos Socrates Mantzoros''' is a Greek American physician scientist, internist - endocrinologist, researcher, [[Harvard Medical School]] professor and the editor-in-chief of the journal [[Metabolism: Clinical and Experimental]]. He is considered a pioneer and worldwide expert in obesity and metabolism. He has given more than 500 lectures nationally and internationally on these critical topics. His research has resulted in more than 600 publications in Medline, more than 145 publications under the collaborative Look Ahead Research Group, more than 170 chapters and reviews and has received more than 50,000 citations (Google Scholar) as well as prestigious awards at national and international meetings.<ref>{{PubMedAuthorSearch|Mantzoros|C}}</ref> He has an H index of 114.<ref>{{cite web|url=https://scholar.google.com/citations?user=PllPdaAAAAAJ&hl|title=Christos Mantzoros - Google Scholar Citations|publisher=}}</ref>


'''Christos S. Mantzoros''' received several prestigious awards in the 2017-2018 academic year. In particular, he received the 2017 Obesity Society TOPS Award, the 2018 Endocrine Society’s Outstanding Clinical Investigator Award, the 2018 European Society of Endocrinology highest distinction, i.e. the Geoffrey Harris Award and the 2018 American Society for Nutrition Robert H. Herman Research Award.<ref>{{cite web|url=https://www.ellines.com/en/good-news/35927-greek-researcher-will-receive-the-top-three-international-awards-in-the-fields-of-endocrinology-and-metabolism/|title=press release for Dr. Mantzoros's 2017-2018 awards|publisher=}}</ref>
'''Christos S. Mantzoros''' received several prestigious awards in the 2017-2018 academic year. In particular, he received the 2017 Obesity Society TOPS Award, the 2018 Endocrine Society’s Outstanding Clinical Investigator Award, the 2018 European Society of Endocrinology highest distinction, i.e. the Geoffrey Harris Award and the 2018 American Society for Nutrition Robert H. Herman Research Award.<ref>{{cite web|url=https://www.ellines.com/en/good-news/35927-greek-researcher-will-receive-the-top-three-international-awards-in-the-fields-of-endocrinology-and-metabolism/|title=press release for Dr. Mantzoros's 2017-2018 awards|publisher=}}</ref>
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== Research ==
== Research ==
His work spans the entire spectrum from animal physiology and molecular biology, through observational, epidemiology studies, to physiology and pharmacokinetic interventional proof-of-concept clinical trials on new therapeutic agents important in the treatment of obesity, diabetes and other metabolic diseases in humans.<ref name="Drie">{{cite web|url=https://www.bidmc.org/research/research-by-department/medicine/endocrinology/laboratories/mantzoros-lab/members/christos-mantzoros-md-dsc-hc-mult-phd|title=Christos Mantzoros, MD, DSc, h.c. mult. PhD|date=2016|publisher=}}</ref> Dr. Christos Mantzoros is known for his groundbreaking work on [[leptin]] (see ''Leptin'' below) and [[adiponectin]] and the relationship between [[IGF-1]] and [[cancer]] (see ''Epidemiology of Cancer'' below). Recent major contributions of his research group include the elucidation of the physiological role and potential diagnostic and therapeutic utility of several adipokines and myokines, leptin, adiponectin, in human physiology and pathophysiology.<ref name="Drie" /><ref>Huh JY, Panagiotou G, Mougios V, Brinkoetter M, Vamvini MT, Schneider BE, Mantzoros CS. FNDC5 and irisin in humans: I. Predictors of circulating concentrations in serum and plasma and II. mRNA expression and circulating concentrations in response to weight loss and exercise. Metabolism. 2012 Dec;61(12):1725-38. {{doi|10.1016/j.metabol.2012.09.002}}. Epub 2012 Sep 25. {{PMID|23018146}}; {{PMC|3614417}}.</ref> Leptin has been approved by the Food and Drugs Administration for lipodystrophy and severe insulin resistance accompanied by hyperglycemia and hyperlipidemia.<ref name="Drie" /> His work has resulted in patents for diagnostic and therapeutic applications and has directly contributed to the development of new pharmaceuticals by major pharmaceutical companies. Currently, he and his team are utilizing various interventions (physiological, pharmacological and dietary) and tools (hormonal, neurocognitive and neuroimaging, [[functional MRI]]) to investigate the role of the human brain in regulating energy homeostasis, obesity and metabolism (See ''Neuroimaging Studies'' below).
His work spans the entire spectrum from animal physiology and molecular biology, through observational, epidemiology studies, to physiology and pharmacokinetic interventional proof-of-concept clinical trials on new therapeutic agents important in the treatment of obesity, diabetes and other metabolic diseases in humans.<ref name="Drie">{{cite web|url=https://www.bidmc.org/research/research-by-department/medicine/endocrinology/laboratories/mantzoros-lab/members/christos-mantzoros-md-dsc-hc-mult-phd|title=Christos Mantzoros, MD, DSc, h.c. mult. PhD|date=2016|publisher=}}</ref> Dr. Christos Mantzoros is known for his groundbreaking work on [[leptin]] (see ''Leptin'' below) and [[adiponectin]] and the relationship between [[IGF-1]] and [[cancer]] (see ''Epidemiology of Cancer'' below). Recent major contributions of his research group include the elucidation of the physiological role and potential diagnostic and therapeutic utility of several adipokines and myokines, leptin, adiponectin, in human physiology and pathophysiology.<ref name="Drie" /><ref name=pmid23018146>{{cite journal |doi=10.1016/j.metabol.2012.09.002 }}</ref> Leptin has been approved by the Food and Drugs Administration for lipodystrophy and severe insulin resistance accompanied by hyperglycemia and hyperlipidemia.<ref name="Drie" /> His work has resulted in patents for diagnostic and therapeutic applications and has directly contributed to the development of new pharmaceuticals by major pharmaceutical companies. Currently, he and his team are utilizing various interventions (physiological, pharmacological and dietary) and tools (hormonal, neurocognitive and neuroimaging, [[functional MRI]]) to investigate the role of the human brain in regulating energy homeostasis, obesity and metabolism (See ''Neuroimaging Studies'' below).


In 2018, Dr. Mantzoros gave a Harvard Medical School Mini Med lecture to teach medical concepts to a lay audience. The lecture was attended by close to 100,000 people from all over the world through live-streaming.<ref>{{cite web|url=https://hms.harvard.edu/news/longwood-seminars|title=HMS Mini Med Lectures|publisher=}}</ref><ref>{{cite web|url=https://www.youtube.com/watch?v=kfTpIicAhp8|title=Mini Med Lecture Video|publisher=}}</ref>
In 2018, Dr. Mantzoros gave a Harvard Medical School Mini Med lecture to teach medical concepts to a lay audience. The lecture was attended by close to 100,000 people from all over the world through live-streaming.<ref>{{cite web|url=https://hms.harvard.edu/news/longwood-seminars|title=HMS Mini Med Lectures|publisher=}}</ref><ref>{{cite web|url=https://www.youtube.com/watch?v=kfTpIicAhp8|title=Mini Med Lecture Video|publisher=}}</ref>


== Leptin ==
== Leptin ==
In the area of leptin, Christos Mantzoros is a world-renowned expert, having pioneered physiology studies, clinical trials in humans and discovering its therapeutic potential. He was the first to investigate the normal physiology of leptin in humans, including circadian rhythms and the role of leptin in fasting and with relation to body weight.<ref>Mantzoros CS, Moschos SJ. Leptin: in search of role(s) in human physiology and pathophysiology. Clin Endocrinol 1998;49:551–567.</ref><ref>Ahima RS, Prabakaran D, Mantzoros C, Qu D, Lowell B, Maratos-Flier E, Flier JS. Role of leptin in the neuroendocrine response to fasting. Nature. 1996 Jul 18;382(6588):250-2. {{PMID|8717038}}.</ref><ref>Mantzoros CS, Moschos SJ. Leptin: in search of role(s) in human physiology and pathophysiology. Clin Endocrinol 1998;49:551–567.\</ref><ref>Chan JL, Heist K, DePaoli AM, Veldhuis JD, Mantzoros CS. The role of falling leptin levels in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men. J Clin Invest 2003;111:1409–1421.</ref><ref name="Acht">Roemmich JN, Clark PA, Berr SS, Mai V, Mantzoros CS, Flier JS, et al. Gender differences in leptin levels during puberty are related to the subcutaneous fat depot and sex steroids. Am J Physiol 1998;275(3 Pt 1):E543–E551</ref><ref name="Negen">Chan JL, Wong SL, Mantzoros CS. Pharmacokinetics of subcutaneous recombinant methionyl human leptin administration in healthy subjects in the fed and fasting states: regulation by gender and adiposity. Clin Pharmacokinet 2008;47:753–764 Link text</ref><ref>Lee JH, Chan JL, Yiannakouris N, Kontogianni M, Estrada E, Seip R, Orlova C, Mantzoros CS. Circulating resistin levels are not associated with obesity or insulin resistance in humans and are not regulated by fasting or leptin administration: cross-sectional and interventional studies in normal, insulin-resistant, and diabetic subjects. J Clin Endocrinol Metab. 2003 Oct;88(10):4848-56. {{PMID|14557464}}.</ref> His team has published the only three studies on leptin pharmacokinetics determining leptin doses to be used in humans. Indeed, his research broadened the understanding of the neuroendocrine function of leptin on body weight, energy homeostasis, gender differentiation, immunology and the interaction with other hormones, such as thyroid stimulating hormone and sex steroids. Observing that hypothalamic amenorrhea (HA) and lipodystrophy were conditions of hypoleptinemia, he piloted clinical trials to test the efficacy of leptin to treat these conditions, showing that leptin replacement in patients with HA and lipodystrophy resulted in complete normalization of hormone axes and bone density in HA as well as insulin resistance and metabolic regulation in lipodystrophy.<ref name="Acht" /><ref name="Negen" /><ref>Welt CK, Chan JL, Bullen J, Murphy R, Smith P, DePaoli AM, Karalis A, Mantzoros CS. Recombinant human leptin in women with hypothalamic amenorrhea. N Engl J Med. 2004 Sep 2;351(10):987-97. {{PMID|15342807}}.</ref><ref>Matarese G, Moschos S, Mantzoros CS. Leptin in immunology. J Immunol. 2005 Mar 15;174(6):3137-42. Review. {{PMID|15749839}}.</ref><ref>Licinio J, Mantzoros C, Negrão AB, Cizza G, Wong ML, Bongiorno PB, et al. Human leptin levels are pulsatile and inversely related to pituitary-adrenal function. Nat Med 1997;3:575–579.</ref><ref>Mantzoros CS, Ozata M, Negrao AB, Suchard MA, Ziotopoulou M, Caglayan S, et al. Synchronicity of frequently sampled thyrotropin (TSH) and leptin concentrations in healthy adults and leptin-deficient subjects: evidence for possible partial TSH regulation by leptin in humans. J Clin Endocrinol Metab 2001;86:3284–3291.</ref><ref>Mantzoros CS. Role of leptin in reproduction. Ann N Y Acad Sci 2000;900:174–183.</ref><ref>Mantzoros C, Flier JS, Lesem MD, Brewerton TD, Jimerson DC. Cerebrospinal fluid leptin in anorexia nervosa: correlation with nutritional status and potential role in resistance to weight gain. J Clin Endocrinol Metab 1997;82:1845–1851.</ref><ref>Chan JL, Mantzoros CS. Role of leptin in energy-deprivation states: normal human physiology and clinical implications for hypothalamic amenorrhoea and anorexia nervosa. Lancet 2005;366:74–85.</ref><ref>Mantzoros CS. Whither recombinant human leptin treatment for HIV-associated lipoatrophy and the metabolic syndrome? J Clin Endocrinol Metab 2009;94:1089–1091.</ref> Additionally, he observed that functional changes in how the brain views food occur in subjects with hypoleptinemia and that these can be corrected with leptin replacement.<ref>Farr OM, Fiorenza C, Papageorgiou P, Brinkoetter M, Ziemke F, Koo BB, Rojas R, Mantzoros CS. Leptin therapy alters appetite and neural responses to food stimuli in brain areas of leptin-sensitive subjects without altering brain structure. J Clin Endocrinol Metab. 2014 Dec;99(12):E2529-38. {{doi|10.1210/jc.2014-2774}}. {{PMID|25279500}}; {{PMC|4255115}}.</ref> Dr. Mantzoros and his team observed that short-term metreleptin treatment enhanced activity in areas detecting the salience and rewarding value of food during fasting, while long-term treatment decreased attention to and the rewarding value of food after feeding. Furthermore, hypothalamic activity is modulated by metreleptin treatment and leptin decreases functional connectivity of the hypothalamus to key feeding-related areas in these hypoleptinemic subjects. These findings expanded the role of leptin into systemic neuroendocrine regulation.
In the area of leptin, Christos Mantzoros is a world-renowned expert, having pioneered physiology studies, clinical trials in humans and discovering its therapeutic potential. He was the first to investigate the normal physiology of leptin in humans, including circadian rhythms and the role of leptin in fasting and with relation to body weight.<ref>{{cite journal |doi=10.1046/j.1365-2265.1998.00571.x }}</ref><ref name=pmid8717038>{{cite journal |pmid=8717038 }}</ref><ref>{{cite journal |doi=10.1046/j.1365-2265.1998.00571.x }}</ref><ref>{{cite journal |doi=10.1172/JCI200317490 }}</ref><ref name="Acht">{{cite journal |doi=10.1152/ajpendo.1998.275.3.E543 }}</ref><ref name="Negen">{{cite journal |doi=10.2165/00003088-200847110-00006 }}</ref><ref name=pmid14557464>{{cite journal |pmid=14557464 }}</ref> His team has published the only three studies on leptin pharmacokinetics determining leptin doses to be used in humans. Indeed, his research broadened the understanding of the neuroendocrine function of leptin on body weight, energy homeostasis, gender differentiation, immunology and the interaction with other hormones, such as thyroid stimulating hormone and sex steroids. Observing that hypothalamic amenorrhea (HA) and lipodystrophy were conditions of hypoleptinemia, he piloted clinical trials to test the efficacy of leptin to treat these conditions, showing that leptin replacement in patients with HA and lipodystrophy resulted in complete normalization of hormone axes and bone density in HA as well as insulin resistance and metabolic regulation in lipodystrophy.<ref name="Acht" /><ref name="Negen" /><ref name=pmid15342807>{{cite journal |pmid=15342807 }}</ref><ref name=pmid15749839>{{cite journal |pmid=15749839 }}</ref><ref>{{cite journal |doi=10.1038/nm0597-575 }}</ref><ref>{{cite journal |doi=10.1210/jcem.86.7.7644 }}</ref><ref>{{cite journal |doi=10.1111/j.1749-6632.2000.tb06228.x }}</ref><ref>{{cite journal |doi=10.1210/jcem.82.6.4006 }}</ref><ref>{{cite journal |doi=10.1016/S0140-6736(05)66830-4 }}</ref><ref>{{cite journal |doi=10.1210/jc.2009-0340 }}</ref> Additionally, he observed that functional changes in how the brain views food occur in subjects with hypoleptinemia and that these can be corrected with leptin replacement.<ref name=pmid25279500>{{cite journal |doi=10.1210/jc.2014-2774 }}</ref> Dr. Mantzoros and his team observed that short-term metreleptin treatment enhanced activity in areas detecting the salience and rewarding value of food during fasting, while long-term treatment decreased attention to and the rewarding value of food after feeding. Furthermore, hypothalamic activity is modulated by metreleptin treatment and leptin decreases functional connectivity of the hypothalamus to key feeding-related areas in these hypoleptinemic subjects. These findings expanded the role of leptin into systemic neuroendocrine regulation.


== Epidemiology of cancer ==
== Epidemiology of cancer ==
Observing that the incidence of certain cancers increases with the rate of obesity (e.g. cancers which have been linked with obesity such as endometrial, esophageal, breast, etc.), Dr. Mantzoros hypothesized that insulin-like growth factor 1 (IGF-1) which is also found at higher levels in obesity and a growth factor might be related to the development of cancer. Indeed, he first confirmed in a case-control study that IGF-1 was linked with prostate cancer.<ref>Wolk A, Mantzoros CS, Andersson SO, Bergström R, Signorello LB, Lagiou P, Adami HO, Trichopoulos D. Insulin-like growth factor 1 and prostate cancer risk: a population-based, case-control study. J Natl Cancer Inst. 1998 Jun 17;90(12):911-5. {{PMID|9637140}}.</ref><ref>Mantzoros CS, Tzonou A, Signorello LB, Stampfer M, Trichopoulos D, Adami HO. Insulin-like growth factor 1 in relation to prostate cancer and benign prostatic hyperplasia. Br J Cancer. 1997;76(9):1115-8. {{PMID|9365156}}; {{PMC|2228109}}.</ref><ref>Wolk A, Andersson SO, Mantzoros CS, Trichopoulos D, Adami HO. Can measurements of IGF-1 and IGFBP-3 improve the sensitivity of [[prostate cancer screening]]? Lancet. 2000 Dec 2;356(9245):1902-3. {{PMID|11130391}}.</ref> Later, he confirmed a similar link between IGF-1 and other types of cancers, including thyroid, breast, and others both in case control and prospective epidemiology studies.<ref name="Eenentwintig"/><ref name="Eenentwintig">[Moschos SJ, Mantzoros CS. The role of the IGF system in cancer: from basic to clinical studies and clinical applications. Oncology. 2002;63(4):317-32. Review. {{PMID|12417786}}.]</ref><ref name="Tweeentwintig">Pazaitou-Panayiotou K, Panagiotou G, Polyzos SA, Mantzoros CS. Serum adiponectin and insulin-like growth factor 1 in predominantly female patients with thyroid cancer: association with the histologic characteristics of the tumor. Endocr Pract. 2016 Jan;22(1):68-75. {{doi|10.4158/EP15814.OR}}. Epub 2015 Oct 20. {{PMID|26484409}}</ref><ref>Larsson SC, Mantzoros CS, Wolk A. Diabetes mellitus and risk of breast cancer: a meta-analysis. Int J Cancer. 2007 Aug 15;121(4):856-62. {{PMID|17397032}}.</ref> This work opened the way for efforts to develop molecules blocking IGF-1 signaling as possible treatments for cancer, currently being tested.
Observing that the incidence of certain cancers increases with the rate of obesity (e.g. cancers which have been linked with obesity such as endometrial, esophageal, breast, etc.), Dr. Mantzoros hypothesized that insulin-like growth factor 1 (IGF-1) which is also found at higher levels in obesity and a growth factor might be related to the development of cancer. Indeed, he first confirmed in a case-control study that IGF-1 was linked with prostate cancer.<ref name=pmid9637140>{{cite journal |pmid=9637140 }}</ref><ref name=pmid9365156>{{cite journal |pmid=9365156 }}</ref><ref name=pmid11130391>{{cite journal |pmid=11130391 }}</ref> Later, he confirmed a similar link between IGF-1 and other types of cancers, including thyroid, breast, and others both in case control and prospective epidemiology studies.<ref name="Eenentwintig"/><ref name="Eenentwintig">{{cite journal |pmid=12417786 }}</ref><ref name=pmid26484409>{{cite journal |doi=10.4158/EP15814.OR }}</ref><ref name=pmid17397032>{{cite journal |pmid=17397032 }}</ref> This work opened the way for efforts to develop molecules blocking IGF-1 signaling as possible treatments for cancer, currently being tested.
Additionally, observing the links between insulin resistance, inflammation, and sex steroids with central obesity and obesity-related cancers, Dr. Mantzoros expanded this research to the molecule [[adiponectin]], hypothesizing that abnormalities in this molecule, caused by abnormal fat deposition in the abdomen, were upstream of all other hormonal and inflammatory abnormalities above. First performing physiology studies in rodents and later in human case-control and prospective cohort studies, his team demonstrated the link between adiponectin and several types of cancer, including breast, colorectal, thyroid, prostate, and others.<ref name="Eenentwintig"/><ref name="Eenentwintig"/><ref name=pmid26484409/><ref name=pmid16859394>{{cite journal |pmid=16859394 }}</ref><ref name=pmid26598515>{{cite journal |doi=10.1093/jnci/djv363 }}</ref><ref name=pmid25833038>{{cite journal |doi=10.1111/eci.12445 }}</ref><ref name=pmid24157941>{{cite journal |doi=10.1530/ERC-13-0240 }}</ref><ref name=pmid24140093>{{cite journal |doi=10.1016/j.metabol.2013.09.007 }}</ref><ref name=pmid23624817>{{cite journal |doi=10.1007/s10549-013-2546-6 }}</ref><ref name=pmid22547160>{{cite journal |doi=10.1210/er.2011-1015 }}</ref><ref name="Dertig">{{cite journal |doi=10.1158/1535-7163.MCT-11-0545 }}</ref><ref name=pmid21937620>{{cite journal |doi=10.1210/jc.2010-1908 }}</ref><ref name=pmid21632074>{{cite journal |doi=10.1016/j.metabol.2011.03.020 }}</ref><ref name=pmid19738128>{{cite journal |doi=10.1200/JCO.2008.19.7525 }}</ref><ref name=pmid19051043>{{cite journal |doi=10.1007/s10552-008-9273-z }}</ref><ref name=pmid18827209>{{cite journal |doi=10.1001/jama.300.13.1523 }}</ref><ref name=pmid18814045>{{cite journal |doi=10.1007/s10552-008-9233-7 }}</ref><ref name=pmid18646046>{{cite journal |doi=10.1002/pros.20823 }}</ref><ref name=pmid18451143>{{cite journal |doi=10.1158/0008-5472.CAN-08-0533 }}</ref><ref name=pmid18045951>{{cite journal |pmid=18045951 }}</ref><ref name=pmid17512191>{{cite journal |pmid=17512191}}</ref><ref name=pmid17213279>{{cite journal |pmid=17213279 }}</ref><ref name=pmid17205522>{{cite journal |pmid=17205522 }}</ref><ref name=pmid16570048>{{cite journal |pmid=16570048 }}</ref><ref name=pmid16404369>{{cite journal |pmid=16404369 }}</ref><ref name=pmid16288122>{{cite journal |pmid=16288122 }}</ref><ref name=pmid15001602>{{cite journal |pmid=15001602 }}</ref><ref name=pmid15001594>{{cite journal |pmid=15001594 }}</ref><ref name=pmid12629074>{{cite journal |pmid=12629074 }}</ref><ref name=pmid21761356>{{cite journal |doi=10.1007/s12672-010-0017-7 }}</ref> This work opened the way for efforts to develop molecules blocking IGF-1 signaling as possible treatments for cancer, currently being tested.
Additionally, observing the links between insulin resistance, inflammation, and sex steroids with central obesity and obesity-related cancers, Dr. Mantzoros expanded this research to the molecule [[adiponectin]], hypothesizing that abnormalities in this molecule, caused by abnormal fat deposition in the abdomen, were upstream of all other hormonal and inflammatory abnormalities above. First performing physiology studies in rodents and later in human case-control and prospective cohort studies, his team demonstrated the link between adiponectin and several types of cancer, including breast, colorectal, thyroid, prostate, and others.<ref name="Eenentwintig"/><ref name="Eenentwintig"/><ref name="Tweeentwintig"/><ref name="auto">Barb D, Pazaitou-Panayiotou K, Mantzoros CS. Adiponectin: a link between obesity and cancer. Expert Opin Investig Drugs. 2006 Aug;15(8):917-31. Review. {{PMID|16859394}}.</ref><ref>Inamura K, Song M, Jung S, Nishihara R, Yamauchi M, Lochhead P, Qian ZR, Kim SA, Mima K, Sukawa Y, Masuda A, Imamura Y, Zhang X, Pollak MN, Mantzoros CS, Harris CC, Giovannucci E, Fuchs CS, Cho E, Chan AT, Wu K, Ogino S. Prediagnosis Plasma Adiponectin in Relation to Colorectal Cancer Risk According to KRAS Mutation Status. J Natl Cancer Inst. 2015 Nov 23;108(4). pii: djv363. {{doi|10.1093/jnci/djv363}}. Print 2016 Apr. {{PMID|26598515}}; {{PMC|4668768}}.</ref><ref name="auto"/><ref>Michalakis K, Venihaki M, Mantzoros C, Vazaiou A, Ilias I, Gryparis A, Margioris AN. In prostate cancer, low adiponectin levels are not associated with insulin resistance. Eur J Clin Invest. 2015 Jun;45(6):572-8. {{doi|10.1111/eci.12445}}. Epub 2015 Apr 24. {{PMID|25833038}}.</ref><ref>Moon HS, Mantzoros CS. Adiponectin and metformin additively attenuate IL1β-induced malignant potential of colon cancer. Endocr Relat Cancer. 2013 Oct 24;20(6):849-59. {{doi|10.1530/ERC-13-0240}}. Print 2013 Dec. {{PMID|24157941}}</ref><ref>Dalamaga M, Karmaniolas K, Chamberland J, Nikolaidou A, Lekka A, Dionyssiou-Asteriou A, Mantzoros CS. Higher fetuin-A, lower adiponectin and free leptin levels mediate effects of excess body weight on insulin resistance and risk for myelodysplastic syndrome. Metabolism. 2013 Dec;62(12):1830-9. {{doi|10.1016/j.metabol.2013.09.007}}. Epub 2013 Oct 17. {{PMID|24140093}}.</ref><ref>Kaklamani VG, Hoffmann TJ, Thornton TA, Hayes G, Chlebowski R, Van Horn L, Mantzoros C. Adiponectin pathway polymorphisms and risk of breast cancer in African Americans and Hispanics in the Women's Health Initiative. Breast Cancer Res Treat. 2013 Jun;139(2):461-8. {{doi|10.1007/s10549-013-2546-6}}. Epub 2013 Apr 30. {{PMID|23624817}}; {{PMC|3773607}}.</ref><ref>Dalamaga M, Diakopoulos KN, Mantzoros CS. The role of adiponectin in cancer: a review of current evidence. Endocr Rev. 2012 Aug;33(4):547-94. {{doi|10.1210/er.2011-1015}}. Epub 2012 Apr 30. Review. {{PMID|22547160}}; {{PMC|3410224}}.</ref><ref name="Dertig">[Moon HS, Chamberland JP, Aronis K, Tseleni-Balafouta S, Mantzoros CS. Direct role of adiponectin and adiponectin receptors in endometrial cancer: in vitro and ex vivo studies in humans. Mol Cancer Ther. 2011 Dec;10(12):2234-43. {{doi|10.1158/1535-7163.MCT-11-0545}}. Epub 2011 Oct 6. {{PMID|21980131}}; {{PMC|3237794}}.]</ref><ref>Mitsiades N, Pazaitou-Panayiotou K, Aronis KN, Moon HS, Chamberland JP, Liu X, Diakopoulos KN, Kyttaris V, Panagiotou V, Mylvaganam G, Tseleni-Balafouta S, Mantzoros CS. Circulating adiponectin is inversely associated with risk of thyroid cancer: in vivo and in vitro studies. J Clin Endocrinol Metab. 2011 Dec;96(12):E2023-8. {{doi|10.1210/jc.2010-1908}}. Epub 2011 Sep 21. {{PMID|21937620}}; {{PMC|3232611}}.</ref><ref>Gialamas SP, Petridou ET, Tseleni-Balafouta S, Spyridopoulos TN, Matsoukis IL, Kondi-Pafiti A, Zografos G, Mantzoros CS. Serum adiponectin levels and tissue expression of adiponectin receptors are associated with risk, stage, and grade of colorectal cancer. Metabolism. 2011 Nov;60(11):1530-8. {{doi|10.1016/j.metabol.2011.03.020}}. Epub 2011 May 31. {{PMID|21632074}}.</ref><ref>Petridou ET, Sergentanis TN, Dessypris N, Vlachantoni IT, Tseleni-Balafouta S, Pourtsidis A, Moschovi M, Polychronopoulou S, Athanasiadou-Piperopoulou F, Kalmanti M, Mantzoros CS. Serum adiponectin as a predictor of childhood non-Hodgkin's lymphoma: a nationwide case-control study. J Clin Oncol. 2009 Oct 20;27(30):5049-55. {{doi|10.1200/JCO.2008.19.7525}}. Epub 2009 Sep 8. {{PMID|19738128}}; {{PMC|2799057}}.</ref><ref>Dalamaga M, Migdalis I, Fargnoli JL, Papadavid E, Bloom E, Mitsiades N, Karmaniolas K, Pelecanos N, Tseleni-Balafouta S, Dionyssiou-Asteriou A, Mantzoros CS. Pancreatic cancer expresses adiponectin receptors and is associated with hypoleptinemia and hyperadiponectinemia: a case-control study. Cancer Causes Control. 2009 Jul;20(5):625-33. {{doi|10.1007/s10552-008-9273-z}}. Epub 2008 Dec 3. {{PMID|19051043}}; {{PMC|2720089}}.</ref><ref>Kaklamani VG, Wisinski KB, Sadim M, Gulden C, Do A, Offit K, Baron JA, Ahsan H, Mantzoros C, Pasche B. Variants of the adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) genes and colorectal cancer risk. JAMA. 2008 Oct 1;300(13):1523-31. {{doi|10.1001/jama.300.13.1523}}. {{PMID|18827209}}; {{PMC|2628475}}.</ref><ref>Dalamaga M, Karmaniolas K, Panagiotou A, Hsi A, Chamberland J, Dimas C, Lekka A, Mantzoros CS. Low circulating adiponectin and resistin, but not leptin, levels are associated with multiple myeloma risk: a case-control study. Cancer Causes Control. 2009 Mar;20(2):193-9. {{doi|10.1007/s10552-008-9233-7}}. Epub 2008 Sep 24. {{PMID|18814045}}.</ref><ref>Sher DJ, Oh WK, Jacobus S, Regan MM, Lee GS, Mantzoros C. Relationship between serum adiponectin and prostate cancer grade. Prostate. 2008 Oct 1;68(14):1592-8. {{doi|10.1002/pros.20823}}. {{PMID|18646046}}.</ref><ref>Kaklamani VG, Sadim M, Hsi A, Offit K, Oddoux C, Ostrer H, Ahsan H, Pasche B, Mantzoros C. Variants of the adiponectin and adiponectin receptor 1 genes and breast cancer risk. Cancer Res. 2008 May 1;68(9):3178-84. {{doi|10.1158/0008-5472.CAN-08-0533}}. {{PMID|18451143}}; {{PMC|2685173}}.</ref><ref>Barb D, Neuwirth A, Mantzoros CS, Balk SP. Adiponectin signals in prostate cancer cells through Akt to activate the mammalian target of rapamycin pathway. Endocr Relat Cancer. 2007 Dec;14(4):995-1005. {{PMID|18045951}}.</ref><ref>Mantzoros CS, Trakatelli M, Gogas H, Dessypris N, Stratigos A, Chrousos GP, Petridou ET. Circulating adiponectin levels in relation to melanoma: a case-control study. Eur J Cancer. 2007 Jun;43(9):1430-6. Epub 2007 May 23. {{PMID|17512191}}.</ref><ref>Tworoger SS, Eliassen AH, Kelesidis T, Colditz GA, Willett WC, Mantzoros CS, Hankinson SE. Plasma adiponectin concentrations and risk of incident breast cancer. J Clin Endocrinol Metab. 2007 Apr;92(4):1510-6. Epub 2007 Jan 9. {{PMID|17213279}}.</ref><ref>Spyridopoulos TN, Petridou ET, Skalkidou A, Dessypris N, Chrousos GP, Mantzoros CS; Obesity and Cancer Oncology Group. Low adiponectin levels are associated with renal cell carcinoma: a case-control study. Int J Cancer. 2007 Apr 1;120(7):1573-8. {{PMID|17205522}}.</ref><ref>Kelesidis I, Kelesidis T, Mantzoros CS. Adiponectin and cancer: a systematic review. Br J Cancer. 2006 May 8;94(9):1221-5. Review. {{PMID|16570048}}; {{PMC|2361397}}.</ref><ref>Petridou E, Mantzoros CS, Dessypris N, Dikalioti SK, Trichopoulos D. Adiponectin in relation to childhood myeloblastic leukaemia. Br J Cancer. 2006 Jan 16;94(1):156-60. {{PMID|16404369}}; {{PMC|2361080}}.</ref><ref>Wei EK, Giovannucci E, Fuchs CS, Willett WC, Mantzoros CS. Low plasma adiponectin levels and risk of colorectal cancer in men: a prospective study. J Natl Cancer Inst. 2005 Nov 16;97(22):1688-94. {{PMID|16288122}}.</ref><ref>Dal Maso L, Augustin LS, Karalis A, Talamini R, Franceschi S, Trichopoulos D, Mantzoros CS, La Vecchia C. Circulating adiponectin and endometrial cancer risk. J Clin Endocrinol Metab. 2004 Mar;89(3):1160-3. {{PMID|15001602}}.</ref><ref>Mantzoros C, Petridou E, Dessypris N, Chavelas C, Dalamaga M, Alexe DM, Papadiamantis Y, Markopoulos C, Spanos E, Chrousos G, Trichopoulos D. Adiponectin and breast cancer risk. J Clin Endocrinol Metab. 2004 Mar;89(3):1102-7. {{PMID|15001594}}.</ref><ref>Petridou E, Mantzoros C, Dessypris N, Koukoulomatis P, Addy C, Voulgaris Z, Chrousos G, Trichopoulos D. Plasma adiponectin concentrations in relation to endometrial cancer: a case-control study in Greece. J Clin Endocrinol Metab. 2003 Mar;88(3):993-7. {{PMID|12629074}}.</ref><ref>Chou SH, Tseleni-Balafouta S, Moon HS, Chamberland JP, Liu X, Kavantzas N, Mantzoros CS. Adiponectin receptor expression in human malignant tissues. Horm Cancer. 2010 Jun;1(3):136-45. {{doi|10.1007/s12672-010-0017-7}}. {{PMID|21761356}}.</ref> This work opened the way for efforts to develop molecules blocking IGF-1 signaling as possible treatments for cancer, currently being tested.


The Mantzoros group also demonstrated a direct effect of adiponectin and adiponectin receptors on endometrial cancer in humans and started mapping the molecular pathways downstream of adiponectin in malignancies.<ref name="Dertig" /> This suggests that adiponectin regulation may be at the root of obesity-related cancers. Due in large part to this research, adiponectin receptor agonists and/or medications that increase circulating levels of adiponectin are currently being tested as a treatment for cancers related to insulin resistance and central obesity.
The Mantzoros group also demonstrated a direct effect of adiponectin and adiponectin receptors on endometrial cancer in humans and started mapping the molecular pathways downstream of adiponectin in malignancies.<ref name="Dertig" /> This suggests that adiponectin regulation may be at the root of obesity-related cancers. Due in large part to this research, adiponectin receptor agonists and/or medications that increase circulating levels of adiponectin are currently being tested as a treatment for cancers related to insulin resistance and central obesity.


== Mediterranean Diet ==
== Mediterranean Diet ==
Dr. Mantzoros also demonstrated that following a Mediterranean Diet, which is high in whole-grain cereals and low-fat dairy products and low consumption of refined cereals, leads to improved levels of adipokines like adiponectin, which decreases insulin resistance, and inflammatory factors like c-reactive protein, and thus leads in the long-term to lower incidence of death from cardiovascular disease and stroke.<ref>Ko BJ, Park KH, Mantzoros CS. Diet patterns, adipokines, and metabolism: where are we and what is next? Metabolism. 2014 Feb;63(2):168-77. {{doi|10.1016/j.metabol.2013.11.004}}. Epub 2013 Nov 12. Review. {{PMID|24360751}}.</ref><ref>Park KH, Zaichenko L, Peter P, Davis CR, Crowell JA, Mantzoros CS. Diet quality is associated with circulating C-reactive protein but not irisin levels in humans. Metabolism. 2014 Feb;63(2):233-41. {{doi|10.1016/j.metabol.2013.10.011}}. Epub 2013 Oct 29. {{PMID|24315778}}; {{PMC|4373656}}.</ref><ref>Mantzoros CS, Sweeney L, Williams CJ, Oken E, Kelesidis T, Rifas-Shiman SL, Gillman MW. Maternal diet and cord blood leptin and adiponectin concentrations at birth. Clin Nutr. 2010 Oct;29(5):622-6. {{doi|10.1016/j.clnu.2010.03.004}}. Epub 2010 Apr 3. {{PMID|20363059}}; {{PMC|2916023}}.</ref><ref>Tsiodras S, Poulia KA, Yannakoulia M, Chimienti SN, Wadhwa S, Karchmer AW, Mantzoros CS. Adherence to Mediterranean diet is favorably associated with metabolic parameters in HIV-positive patients with the highly active antiretroviral therapy-induced metabolic syndrome and lipodystrophy. Metabolism. 2009 Jun;58(6):854-9. {{doi|10.1016/j.metabol.2009.02.012}}. {{PMID|19375132}}; {{PMC|2829239}}.</ref><ref>Fung TT, Rexrode KM, Mantzoros CS, Manson JE, Willett WC, Hu FB. Mediterranean diet and incidence of and mortality from coronary heart disease and stroke in women. Circulation. 2009 Mar 3;119(8):1093-100. {{doi|10.1161/CIRCULATIONAHA.108.816736}}. Epub 2009 Feb 16. Erratum in: Circulation. 2009 Mar 31;119(12):e379. {{PMID|19221219}}; {{PMC|2724471}}.</ref><ref>Yannakoulia M, Yiannakouris N, Melistas L, Kontogianni MD, Malagaris I, Mantzoros CS. A dietary pattern characterized by high consumption of whole-grain cereals and low-fat dairy products and low consumption of refined cereals is positively associated with plasma adiponectin levels in healthy women. Metabolism. 2008 Jun;57(6):824-30. {{doi|10.1016/j.metabol.2008.01.027}}. {{PMID|18502266}}.</ref><ref>antzoros CS, Williams CJ, Manson JE, Meigs JB, Hu FB. Adherence to the Mediterranean dietary pattern is positively associated with plasma adiponectin concentrations in diabetic women. Am J Clin Nutr. 2006 Aug;84(2):328-35. {{PMID|16895879}}.</ref>
Dr. Mantzoros also demonstrated that following a Mediterranean Diet, which is high in whole-grain cereals and low-fat dairy products and low consumption of refined cereals, leads to improved levels of adipokines like adiponectin, which decreases insulin resistance, and inflammatory factors like c-reactive protein, and thus leads in the long-term to lower incidence of death from cardiovascular disease and stroke.<ref name=pmid24360751>{{cite journal |doi=10.1016/j.metabol.2013.11.004 }}</ref><ref name=pmid24315778>{{cite journal |doi=10.1016/j.metabol.2013.10.011 }}</ref><ref name=pmid20363059>{{cite journal |doi=10.1016/j.clnu.2010.03.004 }}</ref><ref name=pmid19375132>{{cite journal |doi=10.1016/j.metabol.2009.02.012 }}</ref><ref name=pmid19221219>{{cite journal |doi=10.1161/CIRCULATIONAHA.108.816736 }}</ref><ref name=pmid18502266>{{cite journal |doi=10.1016/j.metabol.2008.01.027 }}</ref><ref name=pmid16895879>{{cite journal |pmid=16895879 }}</ref>


== Neuroimaging studies ==
== Neuroimaging studies ==
Most recently, Dr. Mantzoros has been working on the interplay of hormones and environmental factors to influence the function of brain centers important in energy homeostasis and metabolism and how these may be altered with pharmaceuticals to treat obesity. Focusing on the human brain, he studies the control of eating behaviors as they are affected in obesity in the human cortex.<ref>Farr OM, Li CS, Mantzoros CS. Central nervous system regulation of eating: Insights from human brain imaging. Metabolism. 2016 May;65(5):699-713. {{doi|10.1016/j.metabol.2016.02.002}}. Epub 2016 Feb 6. Review. {{PMID|27085777}}; {{PMC|4834455}}.</ref> Most significantly, he determined the role of GLP-1 in the human brain. When Dr. Mantzoros and his team examined the GLP-1 analog liraglutide in diabetic adults and found that liraglutide was decreasing activation in the brain's cortex, the area that increases control and makes individuals more attentive to what they are eating.<ref>Farr OM, Sofopoulos M, Tsoukas MA, Dincer F, Thakkar B, Sahin-Efe A, Filippaios A, Bowers J, Srnka A, Gavrieli A, Ko BJ, Liakou C, Kanyuch N, Tseleni-Balafouta S, Mantzoros CS. GLP-1 receptors exist in the parietal cortex, hypothalamus and medulla of human brains and the GLP-1 analogue liraglutide alters brain activity related to highly desirable food cues in individuals with diabetes: a crossover, randomised, placebo-controlled trial. Diabetologia. 2016 May;59(5):954-65. {{doi|10.1007/s00125-016-3874-y}}. Epub 2016 Feb 1. {{PMID|26831302}}; {{PMC|4826792}}.</ref> This suggests that individuals on liraglutide find highly desirable foods less appealing and that the medication might prove an effective weight loss therapy for people who tend to eat foods as a reward, such as when they are stressed. Most recently, Dr. Mantzoros and colleagues examined the serotonin 2c receptor agonist lorcaserin in obese adults and discovered that lorcaserin was decreasing activation in the attention-related parietal and visual cortices in response to highly palatable food cues at 1 week in the fasting state and in the parietal cortex in response to any food cues at 4 weeks in the fed state.<ref>Farr OM, Upadhyay J, Gavrieli A, Camp M, Spyrou N, Kaye H, Mathew H, Vamvini M, Koniaris A, Kilim H, Srnka A, Migdal A, Mantzoros CS. Lorcaserin administration decreases activation of brain centers in response to food cues and these emotion- and salience-related changes correlate with weight loss effects: a four-week-long randomized, placebo-controlled, double-blinded clinical trial. Diabetes. 2016 Jul 6. pii: db160635. [Epub ahead of print] {{PMID|27385157}}.</ref> Decreases in emotion and salience-related limbic activity, including the insula and amygdala, were attenuated at 4 weeks. In a secondary analysis, they observed that decreases in caloric intake, weight, and BMI correlated with activations in amygdala, parietal and visual cortices at baseline, suggesting that lorcaserin would be of particular benefit to emotional eaters. These studies have important implications for obesity and future therapeutics.
Most recently, Dr. Mantzoros has been working on the interplay of hormones and environmental factors to influence the function of brain centers important in energy homeostasis and metabolism and how these may be altered with pharmaceuticals to treat obesity. Focusing on the human brain, he studies the control of eating behaviors as they are affected in obesity in the human cortex.<ref name=pmid27085777>{{cite journal |doi=10.1016/j.metabol.2016.02.002 }}</ref> Most significantly, he determined the role of GLP-1 in the human brain. When Dr. Mantzoros and his team examined the GLP-1 analog liraglutide in diabetic adults and found that liraglutide was decreasing activation in the brain's cortex, the area that increases control and makes individuals more attentive to what they are eating.<ref name=pmid26831302>{{cite journal |doi=10.1007/s00125-016-3874-y }}</ref> This suggests that individuals on liraglutide find highly desirable foods less appealing and that the medication might prove an effective weight loss therapy for people who tend to eat foods as a reward, such as when they are stressed. Most recently, Dr. Mantzoros and colleagues examined the serotonin 2c receptor agonist lorcaserin in obese adults and discovered that lorcaserin was decreasing activation in the attention-related parietal and visual cortices in response to highly palatable food cues at 1 week in the fasting state and in the parietal cortex in response to any food cues at 4 weeks in the fed state.<ref name=pmid27385157>{{cite journal |pmid=27385157 }}</ref> Decreases in emotion and salience-related limbic activity, including the insula and amygdala, were attenuated at 4 weeks. In a secondary analysis, they observed that decreases in caloric intake, weight, and BMI correlated with activations in amygdala, parietal and visual cortices at baseline, suggesting that lorcaserin would be of particular benefit to emotional eaters. These studies have important implications for obesity and future therapeutics.


== Metabolism: Clinical and Experimental ==
== Metabolism: Clinical and Experimental ==
[[Metabolism: Clinical and Experimental]] is a biomedical journal published by Elsevier that promotes excellence in research by publishing high-quality original research papers, fast-tracking cutting-edge papers, research brief reports, mini-reviews, and other special articles related to all aspects of metabolism. Metabolism: Clinical and Experimental publishes studies in humans, animal and cellular models.
[[Metabolism: Clinical and Experimental]] is a biomedical journal published by Elsevier that promotes excellence in research by publishing high-quality original research papers, fast-tracking cutting-edge papers, research brief reports, mini-reviews, and other special articles related to all aspects of metabolism. Metabolism: Clinical and Experimental publishes studies in humans, animal and cellular models.
The journal, one with a distinguished long history in the field of metabolism, was in decline for several years until 2010. Dr. Mantzoros assumed the position of Editor-in-Chief for the journal ''Metabolism: Clinical and Experimental'' in 2010. Under his leadership, the journal has experienced an approximately 20% growth annually in all metrics. The journal's impact factor in 2015 was 4.375 putting it in the top 22% of endocrinology journals (average JIF percentile 78.25%).<ref name="Metabolism Site">[http://www.metabolismjournal.com/]</ref> Its cited half-life was 9.3 in 2015 placing the journal in the top 8% of its category.<ref name="Metabolism Site" /> The impact factor has been continuously increasing over the past six years that he has been serving at the helm, and is now at 5.777 (2016), placing the journal amongst the top 10% of endocrinology, diabetes, and metabolism journals as indexed in Journal Citation Reports. Similarly, cited half-life, or the duration an average paper continues receiving citations, has also increased significantly and in 2016 rose to be in the top 10% of endocrinology, diabetes, and metabolism.
The journal, one with a distinguished long history in the field of metabolism, was in decline for several years until 2010. Dr. Mantzoros assumed the position of Editor-in-Chief for the journal ''Metabolism: Clinical and Experimental'' in 2010. Under his leadership, the journal has experienced an approximately 20% growth annually in all metrics. The journal's impact factor in 2015 was 4.375 putting it in the top 22% of endocrinology journals (average JIF percentile 78.25%).<ref name="Metabolism Site">http://www.metabolismjournal.com/{{full}}</ref> Its cited half-life was 9.3 in 2015 placing the journal in the top 8% of its category.<ref name="Metabolism Site" /> The impact factor has been continuously increasing over the past six years that he has been serving at the helm, and is now at 5.777 (2016), placing the journal amongst the top 10% of endocrinology, diabetes, and metabolism journals as indexed in Journal Citation Reports. Similarly, cited half-life, or the duration an average paper continues receiving citations, has also increased significantly and in 2016 rose to be in the top 10% of endocrinology, diabetes, and metabolism.


== Translation of science into tangible clinical benefits ==
== Translation of science into tangible clinical benefits ==

Revision as of 10:41, 4 July 2018

Christos Socrates Mantzoros

Christos Socrates Mantzoros is a Greek American physician scientist, internist - endocrinologist, researcher, Harvard Medical School professor and the editor-in-chief of the journal Metabolism: Clinical and Experimental. He is considered a pioneer and worldwide expert in obesity and metabolism. He has given more than 500 lectures nationally and internationally on these critical topics. His research has resulted in more than 600 publications in Medline, more than 145 publications under the collaborative Look Ahead Research Group, more than 170 chapters and reviews and has received more than 50,000 citations (Google Scholar) as well as prestigious awards at national and international meetings.[1] He has an H index of 114.[2]

Christos S. Mantzoros received several prestigious awards in the 2017-2018 academic year. In particular, he received the 2017 Obesity Society TOPS Award, the 2018 Endocrine Society’s Outstanding Clinical Investigator Award, the 2018 European Society of Endocrinology highest distinction, i.e. the Geoffrey Harris Award and the 2018 American Society for Nutrition Robert H. Herman Research Award.[3]

Personal

Christos S. Mantzoros was born in Nafplio, Greece and graduated with MD and received a DSc from the University of Athens Medical School. He completed a residency in Internal Medicine at Wayne State University and a fellowship in Endocrinology, Metabolism and Diabetes at the Beth Israel Deaconess Medical Center and Joslin Diabetes Center program of Harvard Medical School. He also received master's degrees in Clinical Epidemiology from the Harvard School of Public Health and Clinical Investigation from Harvard Medical School. He is Board Certified in Internal Medicine and in Endocrinology, Metabolism and Diabetes as well as in Clinical Nutrition. He went rapidly through the academic hierarchy steps from Instructor to Full Professor of Internal Medicine at Harvard University within twelve years.

Research

His work spans the entire spectrum from animal physiology and molecular biology, through observational, epidemiology studies, to physiology and pharmacokinetic interventional proof-of-concept clinical trials on new therapeutic agents important in the treatment of obesity, diabetes and other metabolic diseases in humans.[4] Dr. Christos Mantzoros is known for his groundbreaking work on leptin (see Leptin below) and adiponectin and the relationship between IGF-1 and cancer (see Epidemiology of Cancer below). Recent major contributions of his research group include the elucidation of the physiological role and potential diagnostic and therapeutic utility of several adipokines and myokines, leptin, adiponectin, in human physiology and pathophysiology.[4][5] Leptin has been approved by the Food and Drugs Administration for lipodystrophy and severe insulin resistance accompanied by hyperglycemia and hyperlipidemia.[4] His work has resulted in patents for diagnostic and therapeutic applications and has directly contributed to the development of new pharmaceuticals by major pharmaceutical companies. Currently, he and his team are utilizing various interventions (physiological, pharmacological and dietary) and tools (hormonal, neurocognitive and neuroimaging, functional MRI) to investigate the role of the human brain in regulating energy homeostasis, obesity and metabolism (See Neuroimaging Studies below).

In 2018, Dr. Mantzoros gave a Harvard Medical School Mini Med lecture to teach medical concepts to a lay audience. The lecture was attended by close to 100,000 people from all over the world through live-streaming.[6][7]

Leptin

In the area of leptin, Christos Mantzoros is a world-renowned expert, having pioneered physiology studies, clinical trials in humans and discovering its therapeutic potential. He was the first to investigate the normal physiology of leptin in humans, including circadian rhythms and the role of leptin in fasting and with relation to body weight.[8][9][10][11][12][13][14] His team has published the only three studies on leptin pharmacokinetics determining leptin doses to be used in humans. Indeed, his research broadened the understanding of the neuroendocrine function of leptin on body weight, energy homeostasis, gender differentiation, immunology and the interaction with other hormones, such as thyroid stimulating hormone and sex steroids. Observing that hypothalamic amenorrhea (HA) and lipodystrophy were conditions of hypoleptinemia, he piloted clinical trials to test the efficacy of leptin to treat these conditions, showing that leptin replacement in patients with HA and lipodystrophy resulted in complete normalization of hormone axes and bone density in HA as well as insulin resistance and metabolic regulation in lipodystrophy.[12][13][15][16][17][18][19][20][21][22] Additionally, he observed that functional changes in how the brain views food occur in subjects with hypoleptinemia and that these can be corrected with leptin replacement.[23] Dr. Mantzoros and his team observed that short-term metreleptin treatment enhanced activity in areas detecting the salience and rewarding value of food during fasting, while long-term treatment decreased attention to and the rewarding value of food after feeding. Furthermore, hypothalamic activity is modulated by metreleptin treatment and leptin decreases functional connectivity of the hypothalamus to key feeding-related areas in these hypoleptinemic subjects. These findings expanded the role of leptin into systemic neuroendocrine regulation.

Epidemiology of cancer

Observing that the incidence of certain cancers increases with the rate of obesity (e.g. cancers which have been linked with obesity such as endometrial, esophageal, breast, etc.), Dr. Mantzoros hypothesized that insulin-like growth factor 1 (IGF-1) which is also found at higher levels in obesity and a growth factor might be related to the development of cancer. Indeed, he first confirmed in a case-control study that IGF-1 was linked with prostate cancer.[24][25][26] Later, he confirmed a similar link between IGF-1 and other types of cancers, including thyroid, breast, and others both in case control and prospective epidemiology studies.[27][27][28][29] This work opened the way for efforts to develop molecules blocking IGF-1 signaling as possible treatments for cancer, currently being tested.

Additionally, observing the links between insulin resistance, inflammation, and sex steroids with central obesity and obesity-related cancers, Dr. Mantzoros expanded this research to the molecule adiponectin, hypothesizing that abnormalities in this molecule, caused by abnormal fat deposition in the abdomen, were upstream of all other hormonal and inflammatory abnormalities above. First performing physiology studies in rodents and later in human case-control and prospective cohort studies, his team demonstrated the link between adiponectin and several types of cancer, including breast, colorectal, thyroid, prostate, and others.[27][27][28][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56] This work opened the way for efforts to develop molecules blocking IGF-1 signaling as possible treatments for cancer, currently being tested.

The Mantzoros group also demonstrated a direct effect of adiponectin and adiponectin receptors on endometrial cancer in humans and started mapping the molecular pathways downstream of adiponectin in malignancies.[37] This suggests that adiponectin regulation may be at the root of obesity-related cancers. Due in large part to this research, adiponectin receptor agonists and/or medications that increase circulating levels of adiponectin are currently being tested as a treatment for cancers related to insulin resistance and central obesity.

Mediterranean Diet

Dr. Mantzoros also demonstrated that following a Mediterranean Diet, which is high in whole-grain cereals and low-fat dairy products and low consumption of refined cereals, leads to improved levels of adipokines like adiponectin, which decreases insulin resistance, and inflammatory factors like c-reactive protein, and thus leads in the long-term to lower incidence of death from cardiovascular disease and stroke.[57][58][59][60][61][62][63]

Neuroimaging studies

Most recently, Dr. Mantzoros has been working on the interplay of hormones and environmental factors to influence the function of brain centers important in energy homeostasis and metabolism and how these may be altered with pharmaceuticals to treat obesity. Focusing on the human brain, he studies the control of eating behaviors as they are affected in obesity in the human cortex.[64] Most significantly, he determined the role of GLP-1 in the human brain. When Dr. Mantzoros and his team examined the GLP-1 analog liraglutide in diabetic adults and found that liraglutide was decreasing activation in the brain's cortex, the area that increases control and makes individuals more attentive to what they are eating.[65] This suggests that individuals on liraglutide find highly desirable foods less appealing and that the medication might prove an effective weight loss therapy for people who tend to eat foods as a reward, such as when they are stressed. Most recently, Dr. Mantzoros and colleagues examined the serotonin 2c receptor agonist lorcaserin in obese adults and discovered that lorcaserin was decreasing activation in the attention-related parietal and visual cortices in response to highly palatable food cues at 1 week in the fasting state and in the parietal cortex in response to any food cues at 4 weeks in the fed state.[66] Decreases in emotion and salience-related limbic activity, including the insula and amygdala, were attenuated at 4 weeks. In a secondary analysis, they observed that decreases in caloric intake, weight, and BMI correlated with activations in amygdala, parietal and visual cortices at baseline, suggesting that lorcaserin would be of particular benefit to emotional eaters. These studies have important implications for obesity and future therapeutics.

Metabolism: Clinical and Experimental

Metabolism: Clinical and Experimental is a biomedical journal published by Elsevier that promotes excellence in research by publishing high-quality original research papers, fast-tracking cutting-edge papers, research brief reports, mini-reviews, and other special articles related to all aspects of metabolism. Metabolism: Clinical and Experimental publishes studies in humans, animal and cellular models. The journal, one with a distinguished long history in the field of metabolism, was in decline for several years until 2010. Dr. Mantzoros assumed the position of Editor-in-Chief for the journal Metabolism: Clinical and Experimental in 2010. Under his leadership, the journal has experienced an approximately 20% growth annually in all metrics. The journal's impact factor in 2015 was 4.375 putting it in the top 22% of endocrinology journals (average JIF percentile 78.25%).[67] Its cited half-life was 9.3 in 2015 placing the journal in the top 8% of its category.[67] The impact factor has been continuously increasing over the past six years that he has been serving at the helm, and is now at 5.777 (2016), placing the journal amongst the top 10% of endocrinology, diabetes, and metabolism journals as indexed in Journal Citation Reports. Similarly, cited half-life, or the duration an average paper continues receiving citations, has also increased significantly and in 2016 rose to be in the top 10% of endocrinology, diabetes, and metabolism.

Translation of science into tangible clinical benefits

Dr. Mantzoros consults for several companies as the head of the Mantzoros Consulting, LLC. In 2005, he co-founded Intekrin, Inc. which was later acquired by and merged with Coherus, Inc.[68][69] These companies are developing a number of biosimilars at several stages of clinical development in humans (one approaching FDA approval) in addition to small molecules for diseases related to insulin resistance (e.g. Diabetes, NAFLD). CHRS-131, just successfully completed Phase II trials in humans for Multiple Sclerosis.[70] More recently, Dr. Mantzoros has co-founded Pangea, Inc.

Teaching and Mentoring

Dr. Mantzoros currently serves as the Chief of Endocrinology, Diabetes and Metabolism at the VA Boston Healthcare System and the Director of the Human Nutrition Unit at Beth Israel Deaconess Medical Center. He teaches at Harvard Medical School and Boston University School of Medicine. He has closely mentored more than 125 scientists, 6 of whom are now Full Professors, 1 is now a Chief Medical officer, 1 a Vice President biotechnology companies and several others are currently Assistant and Associate Professors, Executive Directors at pharmaceutical companies or clinicians.

Honors and awards

For his research discoveries and public health service Christos Mantzoros has received four honorary PhDs, the Alexander Technological Institute of Thesaloniki has named their nutrition laboratories after his name, and several universities worldwide have awarded him honorary professorships worldwide and visiting professorships. Also, he has received numerous prestigious awards at national and international meetings, including but not limited to:

  • Clinical Research Award, awarded by the American College of Physicians (1994)
  • Novartis Award in Diabetes, American Diabetes Association Annual Meeting (2005)
  • Friedrich-Wilhelm-Bessel Award of the Humboldt-Foundation, Germany (2005)
  • Frontiers in Science Award, American Association of Clinical Endocrinologists (2006)
  • HypoCCS (Hypopituitary Control and Complications Study) Eli Lilly Award, Paris, France (2006)
  • Lilly Scientific Achievement Award, NAASO, the Obesity Society, Boston, MA (2006)
  • Mead Johnson Award, Experimental Biology, American Society for Nutrition (2006)
  • Mentorship Award for Excellence in Mentoring, Center for Faculty Development, Beth Israel Deaconess Medical Center/ Harvard Medical School (2007)
  • American Society for Nutrition Mead Johnson Award, Washington DC (2007)
  • Election to ASCI (American Society of Clinical Investigation), Chicago, IL (2007)
  • Outstanding Investigator Award, American Federation of Medical Research (2008)
  • Hygeia Award, New England Hellenic Medical and Dental Association (2008)
  • S. Berson Lecture, American Physiological Society (2011)
  • Golden Key Award, City of Nafplion Greece (2012)
  • TOPS Research Achievement Award, Obesity Society (2017)
  • Outstanding Clinical Investigator Award, Endocrine Society (2018)
  • Geoffrey Harris Prize, European Society of Endocrinology (2018)
  • Robert H. Herman Research Award, American Society of Nutrition (2018)

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