It has been suggested that a place a notice here that I have been editing for the first time for the past two weeks, and not using the "minor edit" box correctly. It was not my intent to hide my major edits: I just assumed the wrong meaning of the term. I have also been told there is no way to change this after the fact. I believe what are actually major edits are obvious from the comment box entry. These are accurate.
IiKkEe (talk) 21:28, 25 April 2014 (UTC)
https://en.wikipedia.org/wiki/Wikipedia:Contact_us https://en.wikipedia.org/wiki/Wikipedia:EMPHASIS#Emphasis https://en.wikipedia.org/wiki/WP:Requesting_copyright_permission https://en.wikipedia.org/wiki/WP:Referencing_for_beginners https://en.wikipedia.org/wiki/MOS:DASH
PMC3673773 - Adaptive thermogenesis 100,000 kCal stored in a 70 kg person "Cordinated regulation o energy intake and expenditure mediated by signals emanatin from adipose, gastrointestinal, and endocrine rissues, and integrated by the liver and CNS" lose weight 10% - daily energy enditre goes down 25% -lose 10% wt - gain 20% icrease in skeletal muscle chemomechanicl efficiency,18% gain in FFA use as fuel during light exsrcise PMID12609816 -UCP in BAT yilds more heat generation -BAT activation: ,beta-3 R,THR (thyroid hormone receptor) 19912477 -Leptin sensitive decline in SNS, thyrioid with weight loss COULD BE mechanism of reduced thermog. by BAT -only takes 25G of BAT to explain decline in REE -All of above applies to rodents, noy humans: little BAT im humans: YES THERE IS: BAT in 7.5% womwn, 10% men using PET scans. - Expose to cold: 23/24 have BAT on PET(19357405) - leptin prop to fat mass (8784109corti) -letin conc inv prop to hunger ratings(9822946) -give leptin, hyperphagia goes away (10486419) -Leptin goes down, intake goes up, due to more POMC, less Y(NPY) (AgRP) and (MCH)anorexogenic neuropeptitide POMC; orixigens neuropeptideY, agouti-related peptide, melanin concentrating hormone -leptin gors down,POMC goes down -low leptin meanslow HPT, high HPA -POMC proopiomelaocortin This is it: administration of leptin tolow leptinhumans causes energy expenditure up,energy intake down, SNS up, normalizes HPA, thyroid gonadalfn(11297566)(10486419) -BUT if NoT leptin def,to get a wt loss effect requires dose of L to get L conc overten times normal(10546697) -SUMMARY: lose wt, allsystems attempt to restore wt: metabolic, neuroendocrine,autonomic behavoioiural changes all oppose. FAT STORES ARE DEFENDED BY INTERLOCKINGBIOENERGETCAND NEUROBIOLOGICALPHSIOLOGIES. THe HUMAN BODY ACTIVELY OPPOSES THE CURE. - acponline.org -1999review of1320 papers , No PMID! Perfect diagrams OUTLINE GENETICS REGULATION OF SERUM LEPTIN LEVELS leptin ACTION AND CLEARANCE tHE ROLE OF LEPTIN IN HUMAN PHYSIOLOGY AND PATHOPHYSIOOGY NEONATE cHILHOOD AND PUBERTY← lEPTIN AND LEPTIN RESISTANCE IN HUMAN OBESITY lEPTIN AND THE METABOLIC AND NEUROENDOCRINE RESONSE TO FOOF DEPRIVATION l in hYPERTENSION,←DIABETES,×POLYCYSTIC OVARIAN DISEASE l IN EATING DIRORDERS L IN OTHER CLINICALSRTATES cLINICAL TRIALS FUTURE DIRECTIONS
fROM "The Role of leptin in human Mantzoros obesity and disease 199 Annala vol130 #8
IiKkEe (talk) 01:19, 30 April 2014 (UTC)
MCR - melanocortin
− − Imagawa, et al. Structure-Function Studies of Human Leptin. JBC. 1998, December; 52(273): 35245-35249 y
− Cterminal necessary for secretion, stability, solubility.
− − mammary epithelial cells, bone marrow, pituitary sites of leptin
− − Kline, et al. Leptin is a four-helix bundle: secondary structure by NMR. FEBS Letters.1997, February; 407(2): 239-242 - exhibits a short strand segment and two long random coil loops. Determined secondary structure by NMR. Long chain short helix cytokine fold.
− − Peelman, et al. Mapping of the leptin binding sites and design of a leptin antagonist. JBC. 2004, September; 39(279): 41038-41046 - synthesized first leptin antagonist, caused obesity, altered immune system, hypogonadism. Binding site is the N terminal 94 AA
− − Zhang, F., et al. Crystal Structure of the obese protein leptin-E100. Nature. 1997, May; 387(6629):206-209. First to crystallize. Leptin aggregates so cannot be crystallized
− . Disulfide bonding critical. structure unique
− − Cannot crystallize AA 27-38 As od 2008, don't fully know structure, Rigid hydrophobic core: unique. Core has a hydrophobic cap which buries the lipophilic residues on the the surface of the BD helical bundle