Diet-induced obesity model: Difference between revisions
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=== [[Sedentary lifestyle]] === |
=== [[Sedentary lifestyle]] === |
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[[File:Cushing's syndrome.png|thumb|Symptoms of Cushing's Syndrome]] |
[[File:Cushing's syndrome.png|thumb|Symptoms of Cushing's Syndrome]] |
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Living a sedentary lifestyle is one of the leading factors in causing obesity.<ref> |
Living a sedentary lifestyle is one of the leading factors in causing obesity.<ref>{{Cite journal|last=Wang|first=Chao-Yung|last2=Liao|first2=James K.|date=2012-01-01|title=A Mouse Model of Diet-Induced Obesity and Insulin Resistance|url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3807094/|journal=Methods in molecular biology (Clifton, N.J.)|volume=821|pages=421–433|doi=10.1007/978-1-61779-430-8_27|issn=1064-3745|pmc=3807094|pmid=22125082}}</ref> Today, over 30% of people in the world don't get enough exercise.<ref>[http://www.who.int/dietphysicalactivity/factsheet_inactivity/en/index.html "WHO | Physical Inactivity: A Global Public Health Problem"]. ''[[World Health Organization]]''. Retrieved November 9, 2016.</ref> |
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=== [[Genetics of obesity|Genetic based obesity]] === |
=== [[Genetics of obesity|Genetic based obesity]] === |
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=== Methodology === |
=== Methodology === |
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==== Measures ==== |
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The outcome measure of obesity is usually either the gain of body weight or body fat. The body weight gain is quantified using the difference in the raw mass of the animal or in the Lee index (an index similar to the [[Body mass index|BMI]] in humans). The body fat gain is quantified either indirectly through the weight gain, or directly using [[dual-energy X-ray absorptiometry]]. <ref name=":02">{{Cite journal|last=Hariri|first=Niloofar|last2=Thibault|first2=Louise|date=2010-12-01|title=High-fat diet-induced obesity in animal models|url=https://www.cambridge.org/core/journals/nutrition-research-reviews/article/high-fat-diet-induced-obesity-in-animal-models/AAF3A295061BF9FA5A2347A65D01BBCE|journal=Nutrition Research Reviews|volume=23|issue=2|pages=270–299|doi=10.1017/S0954422410000168|issn=1475-2700}}</ref> When studying effects of obesity on diabetes, a [[Glucose test#Fasting blood sugar|fasting blood sugar]] test is also done before and after the diet. |
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==== Diets ==== |
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Scientists have successfully induced obesity in animals using a wide range of diets. Although generally diets containing more than 30% of total energy from fat are considered to induce obesity, scientists have induced obesity with diets containing 13% to 85% of total energy from fat. The specific fatty foods used in the diets vary across studies, ranging from [[Crisco]] to [[lard]] to [[palm oil]]. <ref name=":02" /> <ref>{{Cite journal|last=Wang|first=Chao-Yung|last2=Liao|first2=James K.|date=2012-01-01|title=A Mouse Model of Diet-Induced Obesity and Insulin Resistance|url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3807094/|journal=Methods in molecular biology (Clifton, N.J.)|volume=821|pages=421–433|doi=10.1007/978-1-61779-430-8_27|issn=1064-3745|pmc=3807094|pmid=22125082}}</ref> |
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<references /> |
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=== Behavioral Changes === |
=== Behavioral Changes === |
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Revision as of 23:29, 10 November 2016
Diet-induced obesity (DIO) model, is a model created to study obesity and its co-morbidities such as type 2 diabetes, hypertension, hypercholesterolemia, atherosclerosis. In this model, an animal (mouse, rat, dog or non-human primate) is fed a high fat diet or high fat/high sugar diet for a number of weeks. As a result, it becomes obese, and usually hyperglycemic, and develops impaired glucose tolerance. These mice are then used to study the genetic and physiological mechanisms of obesity and type 2 diabetes and to test drug candidates that are expected to affect these conditions in humans.
History and Reasons for the Model
| Date | Event |
|---|---|
| September 1978 | First study tested to find correlation between obesity and palatable foods high in fats and lipids, but no conclusion could be reached.
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| 1984 |
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| 1995 |
|
| June 2002 | Göttingen minipig "pilot" study: published paper on a three month long experiment testing a nonrodent model to see if results could be accepted in DIO research or be compared to results of those studies where rodents were tested
|
| 2007 | Continued exploration of diet-induced obesity led to a study of rats as a potential model subject. This genomic based study induced obesity in rats and subsequently analyzed RNA microarrays to characterize the rats metabolic response and resultant insulin sensitivity. |
| 2008 |
|
| 2009 | The model is used to challenge beliefs about the causes of obesity in the population, as a group of scientists decided to test the notion that obesity is a result of overnutrition and could be controlled by limiting meal sizes. |
| 2010 | Continuing the trend of the model’s usage in determining causes of obesity, a group of researchers notice the changes across the diets of several Americans and conduct an experiment to understand why obesity was up when fat consumption was down. For this, they investigate the connection between the types of fat, meal timings and size, and weight gain as well as the reversibility of diet-induced obesity.
|
| July 2011 | Different Diet Stimuli: Diets varying from hyperlipic, hypercaloric, cholesterol-rich, and cafeteria diets were tested on rodents to see which had the most impact on body size and to determine differences between metabolic responses in rodents and humans
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| 2012 | A 2012 study further explored the viability of the diet-induced obesity model by testing several mice for their reactivities to a high-caloric diet. The resulting data found some mice (the B6 mouse) responded to diet-induced obesity most similarly to humans with regards to several parameters including fat content, relative organ size, and general body composition. |
Social Determinants
Social and environmental determinants may also induce the onset of obesity. Social class may affect individual access to proper nutritional education and may hinder an individual's ability to make healthy lifestyle choices. Additionally, samples of low income women and children were also shown to have higher rates of obesity because of stress.[1] Exposure to pollutants such as smoke and second-hand smoke have also shown direct correlations to obesity.
Gut Bacteria
Recent studies on the relationship between infectious agents and weight gain show that certain species of gut flora can affect metabolic processes. This correlation links these gut bacteria to an inability to digest complex polysaccharides. Certain viruses, specifically the AD-36 adenovirus, have been shown to increase body fat in laboratory animals.
Sedentary lifestyle
Living a sedentary lifestyle is one of the leading factors in causing obesity.[2] Today, over 30% of people in the world don't get enough exercise.[3]
Genetic based obesity
Genetic mutations to genes monitoring metabolism and appetite predispose people to obesity. Various syndromes resulting in genetic polymorphisms lead to obesity.[4] A few common examples are: Prader-Willi syndrome, Bardet-Biedl syndrome, Cohen syndrome, and MOMO syndrome.
Other illnesses
Multiple mental and physical illnesses, along with some of the medications that treat such illnesses can increase someone's risk of obesity.[5] Some examples of other illnesses are hypothyroidism, Cushing's syndrome, and growth hormone deficiency.
Limitations
Obesity is affected by “environmental, biological, and psychosocial pressures”[7], therefore it is understandable that several limitations are established when translating results between the results of a diet induced obesity model in a lab and humans. While models are an important method of investigating the influences of obesity and drug testing, it is important to understand the limits of the model's overall ability to resemble the human obesogenic pathophysiology[8]. Such limitations can be divided into three broad categories--biological, experimental, and dietary differences--factors including, but not limited to, the genetic makeup of the species or strain, the environment in which the specimen is held (temperature, light, number of animals), age, sex, the duration of the experiment, and the texture or type of rations fed to the animals[9].
Biological
Numerous sources of biological variation arise in rodents before translating results to humans is even considered. For instance, the age at which mice begin the high-fat diet greatly impacts the metabolic effects.[10] In the strain of mice most commonly used for DIO models, C57BL/6J, mice who started the diet at 10 weeks old showed lower increases in body weight and cholesterol than mice who started at 54 weeks, despite the same diet type and duration.[11] Similarly, 6-week old mice did not develop type diabetes, while 7-8-month old mice did become diabetic due to differences in β-cell activity.[12]
Furthermore, the strain and sex of the rodent impacts the response to the model. Some common mouse strains can show variation in their level of resistance to obesity.[13] Further variation is seen when the sex is also factored in; males of the S5B/P1 strain showed 12% weight gain, while females gained no weight at all.[14] Even within a single strain, large amounts of variation in the phenotype can be seen, despite each mouse having identical genetic backgrounds, which greatly hinders reproducibility.[15]
This has lead to cases of studies that used the same strain of mice concluding that the strain is prone to becoming obese in one study and resistant in the other study.[16][17] So, despite the fact that variability is clearly present in humans, variability in mice is once again detrimental to the reproducibility of results obtained from the diet induced obesity model.[15]
When functional genomics is applied, few commonalities between the gene expression of DIO vs control rodents and obese vs non-obese humans are found.[15][18] This is particularly true in the case of glucose regulation, which greatly hinders the ability to apply the results of the DIO model to humans, especially for drug development.[18][19]
Dietary
Experimental
Research done with model
Methodology
Measures
The outcome measure of obesity is usually either the gain of body weight or body fat. The body weight gain is quantified using the difference in the raw mass of the animal or in the Lee index (an index similar to the BMI in humans). The body fat gain is quantified either indirectly through the weight gain, or directly using dual-energy X-ray absorptiometry. [20] When studying effects of obesity on diabetes, a fasting blood sugar test is also done before and after the diet.
Diets
Scientists have successfully induced obesity in animals using a wide range of diets. Although generally diets containing more than 30% of total energy from fat are considered to induce obesity, scientists have induced obesity with diets containing 13% to 85% of total energy from fat. The specific fatty foods used in the diets vary across studies, ranging from Crisco to lard to palm oil. [20] [21]
- ^ "Obesity and the environment". Wikipedia. 2016-07-01.
- ^ Wang, Chao-Yung; Liao, James K. (2012-01-01). "A Mouse Model of Diet-Induced Obesity and Insulin Resistance". Methods in molecular biology (Clifton, N.J.). 821: 421–433. doi:10.1007/978-1-61779-430-8_27. ISSN 1064-3745. PMC 3807094. PMID 22125082.
- ^ "WHO | Physical Inactivity: A Global Public Health Problem". World Health Organization. Retrieved November 9, 2016.
- ^ Poirier P, Giles TD, Bray GA, Hong Y, Stern JS, Pi-Sunyer FX, Eckel RH (May 2006). "Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss". Arterioscler. Thromb. Vasc. Biol.(Review). 26 (5): 968–76. doi:10.1161/01.ATV.0000216787.85457.f3. PMID 16627822.
- ^ Rosén T, Bosaeus I, Tölli J, Lindstedt G, Bengtsson BA (1993). "Increased body fat mass and decreased extracellular fluid volume in adults with growth hormone deficiency". Clin. Endocrinol. (Oxf). 38 (1): 63–71. doi:10.1111/j.1365-2265.1993.tb00974.x. PMID 8435887.
- ^ "Nutrition & Diabetes - Figure 1 for article: You are what you eat, or are you[quest] The challenges of translating high-fat-fed rodents to human obesity and diabetes". www.nature.com. Retrieved 2016-11-10.
- ^ Giles, Erin D.; Jackman, Matthew R.; MacLean, Paul S. (2016-01-01). "Modeling Diet-Induced Obesity with Obesity-Prone Rats: Implications for Studies in Females". Clinical Nutrition. 3: 50. doi:10.3389/fnut.2016.00050.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ Lai, M.; Chandrasekera, P. C.; Barnard, N. D. (2014-09-08). "You are what you eat, or are you? The challenges of translating high-fat-fed rodents to human obesity and diabetes". Nutrition & Diabetes. 4 (9): e135. doi:10.1038/nutd.2014.30. PMC 4183971. PMID 25198237.
- ^ Reuter, Tanja Y. (2007-01-01). "Diet-induced models for obesity and type 2 diabetes". Drug Discovery Today: Disease Models. Metabolic disorders. 4 (1): 3–8. doi:10.1016/j.ddmod.2007.09.004.
- ^ de Castro, Uberdan Guilherme Mendes; dos Santos, Robson Augusto Souza Augusto Souza; Silva, Marcelo Eustáquio; de Lima, Wanderson Geraldo; Campagnole-Santos, Maria José; Alzamora, Andréia Carvalho (2013-01-01). "Age-dependent effect of high-fructose and high-fat diets on lipid metabolism and lipid accumulation in liver and kidney of rats". Lipids in Health and Disease. 12: 136. doi:10.1186/1476-511X-12-136. ISSN 1476-511X. PMC 3849586. PMID 24044579.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ Korou, Laskarina-Maria A.; Doulamis, Ilias P.; Tzanetakou, Irene P.; Mikhailidis, Dimitri P.; Perrea, Despina N. (2013-10-01). "The effect of biological age on the metabolic responsiveness of mice fed a high-fat diet". Laboratory Animals. 47 (4): 241–244. doi:10.1177/0023677213480768. ISSN 0023-6772. PMID 23760563.
- ^ Tschen, Shuen-Ing; Dhawan, Sangeeta; Gurlo, Tatyana; Bhushan, Anil (2009-06-01). "Age-Dependent Decline in β-Cell Proliferation Restricts the Capacity of β-Cell Regeneration in Mice". Diabetes. 58 (6): 1312–1320. doi:10.2337/db08-1651. ISSN 0012-1797. PMC 2682690. PMID 19228811.
- ^ West, D. B.; Boozer, C. N.; Moody, D. L.; Atkinson, R. L. (1992-06-01). "Dietary obesity in nine inbred mouse strains". The American Journal of Physiology. 262 (6 Pt 2): R1025–1032. ISSN 0002-9513. PMID 1621856.
- ^ Schemmel, R.; Mickelsen, O.; Gill, J. L. (1970-09-01). "Dietary obesity in rats: Body weight and body fat accretion in seven strains of rats". The Journal of Nutrition. 100 (9): 1041–1048. ISSN 0022-3166. PMID 5456549.
- ^ a b c Lai, M.; Chandrasekera, P. C.; Barnard, N. D. (2014-09-08). "You are what you eat, or are you? The challenges of translating high-fat-fed rodents to human obesity and diabetes". Nutrition & Diabetes. 4 (9): e135. doi:10.1038/nutd.2014.30. PMC 4183971. PMID 25198237.
- ^ Andrikopoulos, Sofianos; Massa, Christine M.; Aston-Mourney, Kathryn; Funkat, Alexandra; Fam, Barbara C.; Hull, Rebecca L.; Kahn, Steven E.; Proietto, Joseph (2005-10-01). "Differential effect of inbred mouse strain (C57BL/6, DBA/2, 129T2) on insulin secretory function in response to a high fat diet". Journal of Endocrinology. 187 (1): 45–53. doi:10.1677/joe.1.06333. ISSN 0022-0795. PMID 16214940.
- ^ Fearnside, Jane F.; Dumas, Marc-Emmanuel; Rothwell, Alice R.; Wilder, Steven P.; Cloarec, Olivier; Toye, Ayo; Blancher, Christine; Holmes, Elaine; Tatoud, Roger (2008-02-27). "Phylometabonomic Patterns of Adaptation to High Fat Diet Feeding in Inbred Mice". PLOS ONE. 3 (2): e1668. doi:10.1371/journal.pone.0001668. ISSN 1932-6203. PMC 2244706. PMID 18301746.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ a b Li, Shuyu; Zhang, Hong-Yan; Hu, Charlie C.; Lawrence, Frank; Gallagher, Kelly E.; Surapaneni, Anupama; Estrem, Shawn T.; Calley, John N.; Varga, Gabor (2008-04-01). "Assessment of Diet-induced Obese Rats as an Obesity Model by Comparative Functional Genomics". Obesity. 16 (4): 811–818. doi:10.1038/oby.2007.116. ISSN 1930-739X.
- ^ Chandrasekera, P. Charukeshi; Pippin, John J. (2014-01-01). "Of rodents and men: species-specific glucose regulation and type 2 diabetes research". ALTEX. 31 (2): 157–176. ISSN 1868-596X. PMID 24270692.
- ^ a b Hariri, Niloofar; Thibault, Louise (2010-12-01). "High-fat diet-induced obesity in animal models". Nutrition Research Reviews. 23 (2): 270–299. doi:10.1017/S0954422410000168. ISSN 1475-2700.
- ^ Wang, Chao-Yung; Liao, James K. (2012-01-01). "A Mouse Model of Diet-Induced Obesity and Insulin Resistance". Methods in molecular biology (Clifton, N.J.). 821: 421–433. doi:10.1007/978-1-61779-430-8_27. ISSN 1064-3745. PMC 3807094. PMID 22125082.
Behavioral Changes
Physiological Changes
The main effect of diet-induced obesity in animals fed a high-fat diet is weight gain. In particular, body composition shifts towards more Fat cells. These effects persist even after the diet becomes lower in fat.[1] Accompanying the changes in body composition are changes in hormone balance. High levels of Leptin and Insulin are produced; at the same time, the body becomes resistant to both.[2] Ghrelin levels after meals are consistently lower, leading to more food consumption and reduced fat usage. [2]
References
- ^ Bray, George A.; Paeratakul, Sahasporn; Popkin, Barry M. (2004-12-30). "Dietary fat and obesity: a review of animal, clinical and epidemiological studies". Physiology & Behavior. Dietary Fat and Energy Balance-Myths and Facts. 83 (4): 549–555. doi:10.1016/j.physbeh.2004.08.039.
- ^ a b Hariri, Niloofar; Thibault, Louise (2010-12-01). "High-fat diet-induced obesity in animal models". Nutrition Research Reviews. 23 (2): 270–299. doi:10.1017/S0954422410000168. ISSN 1475-2700.