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Pharmacology

Obesity and Metabolic Syndrome

2016-10-14
21151
Kunming, China, October 14, 2016

Obesity occurs spontaneously in captive adult NHPs, particularly in cynomolgus and rhesus macaques, with proven similarities to man in the distribution pattern and metabolism of adipose tissues making these species excellent models for the condition in humans.  Moreover, the intra-abdominal adipocytes from the cynomolgus macaque are metabolically similar to human adipocytes.  Quantifiable pericardial fat, the secretion of which may directly influence cardiac and coronary vasculature functions, is distinctly observed in macaques in contrast to rodents.  Finally, socio-environmental factors tend to influence adipose tissue distribution similar to humans.  Obesity phenotypes induced by high-fat diet corroborated that, similar to man, NHPs could develop metabolic syndrome. 


Metabolic syndrome, which refers to the co-occurrence of obesity, insulin resistance, dyslipidemia, and hypertension with associated cardiovascular risk factors, affects 20 to 25% of the entire world human population. The close phylogenetic relatedness of monkeys to man with regard to feed responses, lipid-lipoprotein profiles, and genotype make them desirable translational disease models for studying human bioenergetics, obesity, metabolic syndrome, diabetes mellitus, and associated co-morbidities.


KBI has the reputable advantage of having large colonies of naturally-occurring/spontaneous, as well as, diet-induced obese, pre-diabetic/ diabetic and dysmetabolic cynomolgus macaque models that offer translational value for the investigation of pathophysiological pathways and the therapeutic potential of novel pharmacological agents targeting obesity, metabolic syndrome, diabetes mellitus and related comorbidities.


At KBI, diet-responsive colonies of cynomolgus macaques are fed with a proprietary high-fat diet, which closely replicates the Western-type diet.  The HFD-induced obesity phenotypes are similar to man in terms of the central fat distribution pattern as well as, the effects of diet on lipid metabolism, insulin secretion and gluco-regulation.  The obese monkeys characteristically develop insulin resistance and hyperlipidemia.


The following models of obesity and metabolic syndrome in cynomolgus monkeys are available at KBI:
·  Spontaneous/Naturalistic and Diet-Induced Obesity / Metabolic Syndrome
·  Spontaneous and Diet-Induced Insulin Resistance
·  Spontaneous and Diet-Induced Impaired Glucose Tolerance/ Pre-Diabetic Model
·  Naturalistic and Diet-Induced Dyslipidemia, and Atherogenic Dyslipidemia
·  Hypertension


Overall, NHPs have been the preferred model for the study of whole body obesity as well as some aspects of fat distribution.  Multidimensional evaluations including the assessment of whole body and fat composition using Dual Energy X-Ray Absorptiometry (DEXA), anthropometry (BW, BMI, abdominal circumference, skin-fold thickness) and clinical chemistry biochemical parameters are performed at KBI for obesity evaluation and therapeutic efficacy outcome assessment.




    


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