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Diet induced obesity animal models for research: Diet-induced obesity in animal models: points to consider and influence on metabolic markers

Kucera, D. Publication types Review.

Matthew Cox
Monday, May 10, 2021
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  • Such enhanced administration of high-KAA mixture diet modulated lipid synthetic pathway and prevented hepatic steatosis and insulin resistance with the reduction of body weight under the high-fat diet [ 55 ]. Views Read Edit View history.

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  • Some of them include monogenic, polygenic, surgical, seasonal, and other models of obesity.

Diabetes Insulin Resistance

Furthermore, agonistic compound for TGR5, INT, mimics such metabolic effect of BAs and inhibited the onset of steatosis in high-fat-fed mice [ 52 ]. Current Protocols in Pharmacology. Metabolic disorders. Although ZFR also exhibits marked insulin resistance [ 36 ], their blood sugar levels remain normal [ 37 ].

Experimental rodent models of type 2 diabetes: a review. J Biomed Biotechnol ; : Received : 24 February Lab Anim.

This review fof aims at analyzing the various animal models of inducing obesity, their advantages, and limitations. Several animals have been in the limelight of basic research associated with metabolic diseases like obesity. Goldman, and M. Lipids Health Dis ; 12 : Accumulating evidence suggests that metformin reduces cancer incidence in type 2 diabetic patients.

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Research use: General studies, Immunology, Oncology, Transplantation, Adjuvant-induced arthritis, Experimental allergic encephalomyelitis. Handb Exp Pharmacol. Research use: Accelerated senescence studies, Age-dependent disorders, Brain atrophy, Deficits in learning and memory, Emotional disorders Aging process, Geriatric pathogenesis, Hearing impairment, Hyperinflation of the lungs, Senile amyloidosis apolipoprotein A-IISenile osteoporosis.

Mitchell, and E. This does not mean, however, that these models can provide information on how obesity can cause other health problems. Single-species versus dual-species probiotic supplmentation as an emerging therapeutic strategy for obesity. Arq Bras Endocrinol Metabol. Vertino, and F. Taylor, S.

Atkinson, W. The WFR strain is widely used for research in type 2 diabetes because aged WFR displays diabetic complications such as nephropathy and neuropathy [ 41 — 44 ]. Rhesus monkeys raised in cages tend to have increased body weights and develop obesity with its comorbidities [ 42 ]. Help Learn to edit Community portal Recent changes Upload file. Epigenetic considerations in obesity Epigenetics is the alteration in a chromosome that damages the activity of a gene for which its expression can be inheritable by offspring.

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Research use: Accelerated senescence studies, Age-dependent disorders, Brain atrophy, Deficits in learning and memory, Emotional disorders Aging process, Geriatric reaearch, Hearing impairment, Hyperinflation of the lungs, Senile amyloidosis apolipoprotein A-IISenile osteoporosis. The Western pattern diet, rich in sugar, fat and ultra-processed foods leads to changes in intestinal permeability, which results in an increase in endotoxemia, insulin resistance, steatosis and inflammation of the adipose tissue [ 3839 ], which results in obesity development [ 363839 ]. Bultman, and S. It can also interfere with other cell signalling pathways as well as affects the content of certain isozymes in organs like liver, brain and kidneys.

Nine studies [ 151617181920212223 ] did not provide the composition of the macronutrients directly, which made it difficult to calculate the amount of calories from fat. The lethal yellow mutant mouse A y is one of five dominant agouti mutations and has been found to be an excellent mouse model of obesity [ 5 ]. Academic Press. Flowchart for selecting articles. Mice without lymphotoxin alphalymphotoxin betaor a lymphotoxin beta receptor gained less weight on a high-fat diet than wild type mice did, even after remaining on a high-fat diet for a prolonged period of time. The influence of the gut microbiome on obesity, metabolic syndrome and gastrointestinal disease. Kemnitz, and C.

Int J Physiol Pathophysiol Pharmacol. Megirian, J. Taxation of sugar-sweetened beverages for reducing their consumption and preventing obesity or other adverse health outcomes. The study also checked for the effects of diabetes on the gene expression. Furthermore, some of the strains exhibit obesity with severe insulin resistance and glucose intolerance, whereas others are highly sensitive to insulin-mediated glucose uptake and are resistant to the onset of diabetes Table 1 [ 507475 ]. Retrieved Abstract Several animals have been in the limelight of basic research associated with metabolic diseases like obesity.

Quantification of abdominal fat depots in rats and mice during obesity and weight loss interventions. There is significant variation in the results appearing in either experimental rodents that were fed with high fat diets made up from different ingredients and from purified ingredient. Suzuki, S. ISSN

Animal Models of Human Pathology

Brown adipose tissue: A human perspective. Rene Gonzalez, A. Journal of Chronic Diseases. E—E,

Similarly, mice with serotonin receptor 5-HT-2c knockout that have a smaller number of functional 5-HT2C receptors develop hyperphagia [ 84 obfsity, 85 ] in which adiposity and body weight are increased during weaning. In this way, some of the evaluated studies noticed obesity animal increase in the serum concentration of ressarch [ 12916172122232535516163 ] and cholesterol [ 291623272935516163 ] in the groups fed with DIO. Diet-induced model of obesity Diet-induced obese DIO rats develop obesity when given HFD, while diet-resistant rats have body weights like control rats when fed with a low energy diet. Guh, W. This paper also addresses future directions necessary to conduct transnationally relevant human obesity and T2DM research. Nat Genet ; 37 : — Therefore, any study that used other ways to induce obesity was excluded.

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Alzheimer's disease, Dementia, Memory loss, Neurodegeneration, Neuroscience, Synaptic formation and repair. Matsuoka, Y. Fernette, E. Ordering Ordering and services Online order initiation form. Nutr Res.

Montez, K. Robledo, C. Obesity is associated with premature death through increasing the risk of many chronic diseases, including type 2 diabetes, cardiovascular disease, and certain cancers Figure 1 [ 34 ]. Lee, J. Nat Rev Endocrinol. Lipids in Health and Disease.

  • Obesity can also be induced by the extensive lesions of the PVN, which eventually may result in hyperinsulinemia and insulin resistance in rats [ ].

  • Gut microbiota: a new path to treat obesity.

  • For example, intestinal microbiome gene profile has been shown to differ between lean and obese individuals on different diets, and the human gut microbial profile has been linked to human insulin action. NIRKO mice take moderate food, resulting in increased body weight, adiposity, hypertriglyceridemia, and high insulin level [ 88 ].

  • Some of them include monogenic, polygenic, surgical, seasonal, and other models of obesity.

Jhanwar, C. Cre tm1Sage. Michaud, and R. This scenario occurs since the increase in acetate stimulates the activation of the parasympathetic pathway, which increases the secretion of ghrelin stimulating both an increase in food consumption and a greater secretion of insulin [ 42 ].

Body weight and fat gain, as well as determinants related to inflammation, hormonal concentration, blood glycemia, lipid profile, and liver health, must be evaluated together to better determination of the development of obesity. The search for articles was carried out manually on PubMed database by a single researcher in February Saitoh, M. With varied sources and types of fat, researches have shown the complexity of defining a model of a high fat diet that can both resemble human meals and accurately quantify the nutrient contents. Male animals are commonly used in the study of obesity; however, if the study aims to evaluate the brown adipose tissue, females should be used, since this tissue is more easily observed in this sex [ 5051 ]. This information suggests that like human obesity, obesity in NZO mice is due to a combination of hyperphagia, reduced energy expenditure, and insufficient physical activity.

BioMed Research International

Obesity in the paleolithic era. Azilsartan treatment improves insulin sensitivity in obese spontaneously hypertensive Koletsky rats. However, the benefit of this model is influenced by the absence of instruments to investigate a genetic basis, and the animals present a huge challenge with regards to setting up research facility-based colonies for the experiments. Nature ; doi Saitoh, M.

Burlet, and S. S2CID Very reliable and effective Avoid effect of cytotoxic chemicals on other body organs. International Journal of Obesity.

Researchers have created the study models of high carbohydrate and high proteins. Different times of intervention, diets, types vor fat and carbohydrates, animal strains, and sex, among others, are used in the studies, which makes it difficult to compare the results and to better evaluate and determine the best way to induce obesity in an animal model. View at: Google Scholar H. Kayo, T. Bipolar disorder, Neuronal growth and transport studies, Neuroscience, Schizophrenia. This does not mean, however, that these models can provide information on how obesity can cause other health problems.

Find research models

Surgical services Toxicology. Rene Gonzalez, A. Diet induced-obesity DIO animal researvh can reproduce human overweight and obesity, and there are many protocols used to lead to excess fat deposition. The micronutrients, fiber and other ingredients must remain the same in order to observe how a specific macronutrient influences or not the outcome of obesity.

  • View at: Google Scholar N. The mental, emotional and cultural factors along with insulin resistance and hyperphagia are known to increase the occurrence of type 2 diabetes in humans.

  • Such enhanced administration of high-KAA mixture diet modulated lipid synthetic pathway and prevented hepatic steatosis and insulin resistance with the reduction of body weight under the high-fat diet [ 55 ].

  • Nine studies [ 151617181920212223 ] did not provide the composition of the macronutrients directly, which made it difficult to calculate the amount of calories from fat.

The appearance of diabetes in WFR but not in ZFR, despite the presence of the fa leptin receptor mutation in both wnimal, could be explained by the presence of other genetic factors in WFR. Burlet, P. Low insulin; more glucose tolerance than other strains on a high-fat diet [ ]. Thibault Published Biology, Medicine Nutrition research reviews Epidemiological studies have shown a positive relationship between dietary fat intake and obesity.

  • Considerations in the design of hyperinsulinemic-euglycemic clamps in the conscious mouse. Ollmann, L.

  • These body alterations may lead to deactivation of liver and mesenteric genes responsible for beta-oxidation [ 25 ]. Research use: Alzheimer's disease, Alzheimer's disease, Neurodegenerative diseases, Neuroscience.

  • Little evidence is currently available on this topic, but some seminal results have been shown []. Transgenic model of obesity To understand the mechanism, transgenic models of obesity have been created.

  • The composition of the diet and calorie overconsumption are also relevant to the development of obesity.

  • Contract breeding Diet-induced obesity Genetic testing.

Eubiosis and dysbiosis: the two sides of the microbiota. Dietary-induced obesity: effect of dietary fats on adipose tissue cellularity in obesit. Metformin treatment inhibits high-energy diet-stimulated colon cancer cell growth [ 90 ] and breast tumor growth in HFD-fed mice but did not inhibit tumor growth in mice fed normal chow [ 91 ]. Accepted : 02 March Influence of gut microbiota on subclinal inflammation and insulin resistance.

Evid Based Complement Alternat Med ; : So far, most lesions are involved the whole mediobasal hypothalamus, involving the ventromedial area. Furthermore, obesity associated diet induced obesity animal models for research dysbiosis is characterized by a low microbial diversity and an imbalance between the different microorganisms of the intestinal microbiota, with a large number of pathogenic bacteria [ 83639 ]. Rats are used in DIO studies Table 2. Increased adipocytes have detrimental consequences on the pancreas, liver, kidneys, brain, heart, reproductive organs, muscles, and joints. Lipids in Health and Disease.

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Research use: Alzheimer's disease, Dopaminergic cell toxicity, Neuroscience. Tumor growth. Megirian, J. Nutrition Research Reviews.

Parsons, and H. Although these dog, pig, and rat models help improve our understanding of the pathophysiology of OSA, mouse models are critical in identifying the genes conferring disease risk [ ]. Saxon, M. View at: Google Scholar S. Phoenix, F. Sridhar Radhakrishnan, Ph. After the exclusion of articles that were duplicated, articles were considered eligible for reading titles and abstracts.

For instance, casein causes more weight reesearch compared to soy. HFD-induced metabolic perturbations: sex, age and strain-dependence The commonly reported T2DM-related metabolic perturbations induced by HFD in rodents include weight gain and increased carcass lipid content, higher degree of insulin resistance and increased levels of plasma glucose, insulin, leptin, cholesterol and triglycerides. Kudo, M. Issue Date : September Pharmacol Res ; 52 : — Schwartz, S.

BioMed Research International

Animal Models of Dietary-Induced Obesity. KDs restrict carbohydrate consumption in order to limit circulating levels of glucose and, therefore, promote production and utilization of ketone bodies as a primary fuel source. It was found that obesity had a stimulating effect, increasing blood pressure and increasing the risk of hypertension. Produced in: France Cryopreserved.

J Lipid Res ; 46 : — Leptin as a mediator of obesity-induced hypertension. View at: Google Scholar W. Pickup, J. Weight put on during the high-fat diet also tends to persist.

Since many types of cancer can be affected by environmental factors, having control over these factors is key to generating reproducible, meaningful data. In Wistar rats the consumption of a high-fat diet appears to lead to an increase in the number of fat cells hyperplasia in the subcutaneous adipose fat, whereas in the visceral adipose fat greater hypertrophy of the adipose tissue is observed [ 60 ]. Diet Induced Metabolic Syndrome. Jolly, and J. Ovary transplant and ova transfer studies, Production of targeted mutations due to the availability of several lines of embryonic stem cells. To study the development of obesity and its risk factors, researchers use diet-induced obesity animal models, since these models reproduce with greater reliability human obesity in comparison with genetic models [7].

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Taylor, S. The Netherlands. This genomic based study induced obesity in rats and subsequently analyzed RNA microarrays to characterize the rats metabolic response and resultant insulin sensitivity. Visceral fat is the depot that surrounds the abdominal organs. Mol Nutr Food Res.

This scenario occurs since the increase in acetate stimulates the activation of the parasympathetic pathway, which increases the secretion of ghrelin stimulating both an increase in food consumption and a greater secretion of insulin [ 42 ]. Nakamura and K. Later, this model was found to exhibit sleep apnea syndrome [ ]. Zhang et al. Ehrich, J. Scientists have successfully induced obesity in animals using a wide range of diets.

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Effects of high-fat diet feeding on Znt8-null mice: differences between beta-cell and global knockout of Znt8. Animal models in type 2 diabetes research: an overview. Requires technical know how. Sapolsky, J. HFD: major limitations to human translatability HFD-feeding: effect of dietary components A wide variety of methods are utilized in HFD studies, with no single method being comparable to the human experience. Lipidosis and swelling of hepatocyte mitochondria in the liver are found in HS rats [ 97 ]. Leptin- and leptin receptor-deficient rodent models: relevance for human type 2 diabetes.

Kluge, S. Advantage Business Media. Table 3 Changes in markers related to body weight and adipose tissue depots Full size table. Evaluation of excess significance bias in animal studies of neurological diseases. Table 1.

Author information Article notes Copyright and License information Disclaimer. Boozer, D. Toye, J. Obstructive sleep apnea OSA is an important obesity-associated health problem that is characterized by obstruction of the airway and depletion of oxygen tone in the blood.

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Zucker and H. International Diabetes Federation: Brussels, Belgium, J Nutr Metab ; :

The increased number of fat cells persists even after the diet becomes lower in fat. Amarsi, C. Research use: Alzheimer's disease, Dopaminergic cell toxicity, Neuroscience. Research models Research models We offer you the experience, quality, and consistency that is essential to your success. After the exclusion of articles that were duplicated, articles were considered eligible for reading titles and abstracts. Michaud, S. In this way, Matias et al.

Bartucci et al. S—S, Nature Immunology. Research Feed. Rodents are nocturnal and are mostly feeding at night, in their natural habitat. This ectopic accumulation researc as a consequence of the downregulation of AMPK [ 3561 ] and upregulation of SREBP-1c [ 61 ], which generates lipogenesis, and increases the synthesis of fatty acids by the liver [ 23 ]. Increased body weight, fat and food intake; both males and females develop hyperinsulinemia; only males develop moderate hyperglycemia [ 29 ].

Introduction

The researchers inducwd that Goishi tea prevented the growth of adipocytes and prevented changes caused by tumor necrosis factor alpha and interleukin 6 when the mice were on a high fat diet. A sense of time: how molecular clocks organize metabolism. As shown on Table 2these studies reported age- sex- strain- and diet-dependent phenotypic variability for example, glucose tolerance, insulin secretion, body weight, etc.

  • There is significant variation in the results appearing in either experimental rodents that were fed with high fat diets made up from different ingredients and from purified ingredient.

  • Figure 1.

  • Brown, K.

  • Kurosumi, and T.

ISBN OSA may be associated with the onset of hypertension, diabetes, and coronary heart disease. It is worthy to note here that each polygene only contributes a fraction to the build-up of obesity [ 59 ]. Neuropeptide Y receptor gene expression in the primate amygdala predicts anxious temperament and brain metabolism. Thus, the increase in the concentrations of both aminotransferases can be associated with the increase in liver weight as well as to hepatic steatosis [ 25 ]. View at: Google Scholar S. J Mol Endocrinol.

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Curr Protoc Pharmacol. Ainul Bahiyah Abu Bakar co-operated in writing and proofreading the paper. Diabetes Care ; 30 : — According to Blancas-Velasquez et al. Obesity and type modells diabetes mellitus T2DM are rapidly growing worldwide epidemics with major health consequences. In this scenario there is lower production of short-chain fatty acids SCFA, like acetate, propionate and butyrate which leads to less protection of the intestinal epithelium, since SCFA are related to occludin and zonulin, and also leads to a drop in the production of glucagon-like peptide-1 GLP-1 resulting in decreased satiety and increased insulin resistance, inflammation and lipid accumulation [ 24384041 ]. Cancer Prevent Res.

References 1. York, K. Help Learn to edit Community portal Recent changes Upload file. Houten, and S. ISBN

Dietary obesity in nine inbred mouse strains. However, animal models have not yet been established for some devastating obesity-associated human diseases, including polycystic ovary syndrome [], which is extremely prevalent and constitutes one of the most common endocrinopathy in women of reproductive age. Obstructive sleep apnea OSA is an important obesity-associated health problem that is characterized by obstruction of the airway and depletion of oxygen tone in the blood. PMC Pickup, J.

Animal Models of Human Pathology

Models oebsity obesity with type 2 diabetes are classified into two categories: 1 those containing a mutation in the leptin or leptin receptor gene and 2 polygenic models. Eisenstein, and I. This inflammatory condition contributes to models for development of metabolic disorders [ 135 ], such as diabetes [ 27 ]; to a decrease in lymphatic function and cutaneous hypersensitivity [ 34 ]; and to the occurrence of other diseases, such as periodontitis [ 62 ] and respiratory allergies [ 63 ]. As there are no cutoff points for any of these parameters in animals, researchers should always conduct their studies with a non-obese control group so that the results can be compared. Table 1.

High-carbohydrate diets can be used alone or in combination with a HFD. Chalkiadaki Duet, Guarente L. It is evident that animals introduced to HFD usually develop obesity and can exhibit reduce levels of insulin and leptin sensitivity [ 94 ]. Mechanisms of obesity-induced hypertension. Increased adipocytes have detrimental consequences on the pancreas, liver, kidneys, brain, heart, reproductive organs, muscles, and joints. Lipids Health Dis ; 12 :

Smith, P. Porte, R. CaspersNicole WormsAswin L. Endocrinology ; 31 : 42— EnriquezAmy D. Banks, J.

Single-species inducd dual-species probiotic supplmentation as an emerging therapeutic strategy for obesity. Type 2 diabetes is associated with insulin resistance and is one of the most common metabolic diseases. Nutr Res Pract. The researchers found that the mice injected with propolis had less adipose tissueglucoseand cholesterol than the mice who were not administered propolis.

Scientists used mice to study the effect of lymphotoxins on metabolism. Eisenstein, and I. One such characteristic is insulin resistancewhich comes with diet-induced obesity in both rats and humans. Polygenic obesity in humans. Reduced renal sympathetic nerve activity improves glucose tolerance in hypothalamus-specific POMC knockout mice by elevating glycosuria.

Mice aged 6 to 8 weeks can be considered young adult mice [ 15 ]. Smith, P. Kucera, D. Hyperinsulinemia is observed beginning at 8 weeks of age, and insulin resistance is observed beginning at 12 weeks of age.

Introduction

Feinglos, C. In this way, some of the evaluated studies noticed an increase in the serum concentration aninal triglycerides [ 12916172122232535516163 ] and cholesterol [ 291623272935516163 ] in the groups fed with DIO. Ovary transplant and ova transfer studies, Production of targeted mutations due to the availability of several lines of embryonic stem cells.

Research use: Behavior, Carcinogenesis, General studies, Teratogenesis. Male TSOD mice exhibit polygenic obesity with hyperglycemia and hyperinsulinemia [ 2627 ]. Overweight and obesity are a worldwide public health problem. Diabetes Metab Syndr Obes. Obesity is associated with various health conditions in humans.

Commonly used in medical research, rats were specifically chosen to study the diet-induced obesity model because of the features that they share with humans. The ketogenic diet KD was originally developed in the early s as a treatment for pediatric epilepsy. Stubbs, L. The beginning stages include simple hepatic steatosis, which is characterized by fat droplet accumulation in hepatocytes and this is usually benign and asymptomatic. J Med Food. Kuhn, C.

Additionally, the mitochondria of the brown adipose tissue are also affect by DIO impairing glucose metabolism [ 51 ]. Saeedi, H. OLETF rats are widely used in obesity and diabetes research. The intervention time required for the development of obesity varies widely, ranging from 8 days to 27 weeks Table 2. Main article: Infectobesity. About this article.

World Moedls Gastroenterol. In addition, streptozotocin and alloxan can cause extrapancreatic genotoxic and cytotoxic effects, including the disruption of the hypothalamic—pituitary—gonadal axis 6364 and changes in hyperglycemia-unrelated hepatic gene expression, 65 making it difficult to distinguish the effect caused by pancreatic cytotoxicity from those caused by extrapancreatic sites. Ethics declarations Competing interests The authors declare no conflict of interest.

Correspondence Mahaneem Mohamed, Email: ym. The study also checked for the effects of diabetes on the gene expression. Established and emerging strategies to crack the genetic code of obesity. The micronutrients, diet induced obesity animal models for research and other ingredients must remain the same in order to observe how a specific macronutrient influences or not the outcome of obesity. The advantages and limitations of animal models of obesity based on technical know-how, duration, life cycle, cost, effectiveness, shape, mortality rate, characterization, complexity, approved facilities, ability to form colonies, time consumption, standardization, and ability to represent human diseases are summarized in Table 3.

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Department of Agriculture and U. J Biomed Biotechnol ; : Diabetes Metab Syndr Obes. Cell Metab ; 7 : In fact, the biggest difficulty to find an effective model for DIO is the lack of standardization among obesity-inducing protocols.

There high fat diet experiments that have been done in rodents realizing the difficulties in interpreting the literature composition of high fat diet into actual experiment. Brennick, S. View at: Google Scholar G. Accumulating evidence suggests that metformin reduces cancer incidence in type 2 diabetic patients.

Main article: Infectobesity. Kuhn, C. Soy protein ameliorates metabolic abnormalities in liver and adipose tissue of rats fed a high fat diet. Transgenic Mice Genetic Very reliable and effective Targeted at a particular gene There are available genetic tools Requires technical know how 4. Spironolactone improves glucose and lipid metabolism by ameliorating hepatic steatosis and inflammation and suppressing enhanced gluconeogenesis induced by high-fat and high-fructose diet.

Solerte, C. About this article. Banks, J. O'Brien, A. These animals can then be used to study in vivo obesity, obesity's comorbiditiesand other related diseases. Wilkinson, W. Melatonin expression in periodontitis and obesity: An experimental in-vivo investigation.

  • S2CID

  • Higashino, and A.

  • Ppopulation, However, it is clear that the natural history and metabolic characteristics of the human condition cannot be effectively recapitulated in a single model or even a combination of these animal models.

  • Monogenic models of obesity.

  • Robledo, C.

Ameliorative potential of ohesity Promising modulation of inflammatory factors and lipid marker enzymes expressions in HFD induced obesity in rats. Quantification of abdominal fat depots in rats and mice for research obesity and weight loss interventions. Dowling, M. Hyperinsulinemia is observed beginning at 8 weeks of age, and insulin resistance is observed beginning at 12 weeks of age. The results of the study illustrate that the high fat diet rats had a higher adiposity index than the low fat diet rats. Consult with one of our scientists on a custom formula for your study.

The plastic surgeon in the treatment of obesity. Selective breeding for diet-induced obesity and resistance in Sprague-Dawley rats. Metformin treatment has been shown to result in a mkdels expression profile similar to that of long-term caloric restriction [ 87 ], which can reduce the incidence of many age-related diseases, including cancer [ 8889 ]. Obesity animal models have also led to the studies of potential drugs and natural products in the management of obesity. Azilsartan treatment improves insulin sensitivity in obese spontaneously hypertensive Koletsky rats. Sapolsky, J. Biochem J ; : —

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