Obesity occurs spontaneously in captive monkeys with similar characteristics to humans in the fat distribution pattern and adipocyte biology. such as pericardial fat which affects cardiac and coronary vasculature functions and central obesity. Central obesity is closely associated with the metabolic syndrome which affects 20 to 25% of human population. The metabolic syndrome also includes insulin resistance, dyslipidemia, fatty liver and hypertension and it is a major risk factor for diabetes and cardiovascular disease.
KBI has large colonies of cynomolgus macaque models of spontaneous and diet-induced obese with a wide range of metabolic disorders including metabolic syndrome, diabetes and other related comorbidities. The diet-responsive colonies of obese cynomolgus macaques induced by KBI proprietary Western-type of high fat diet (HFD). In these monkeys, our HFD predominantly incudes central obesity and the metabolic syndrome effects with a greater propensity to diabetes, non-alcoholic fatty liver disease, cardiovascular disease and chronic kidney disease. The following models of obesity and metabolic syndrome in cynomolgus monkeys are available at KBI:
· Spontaneous and diet-induced obesity with typical phenotype of the metabolic syndrome
· Spontaneous and diet-induced insulin resistance
· Spontaneous and diet-induced impaired glucose tolerance (pre-diabetic model)
· Spontaneous and diet-induced atherogenic dyslipidemia
· Spontaneous and diet-induced hypertension
KBI has a range of tools for the characterization of whole body and fat composition including dual energy X-ray absorptiometry (DEXA), anthropometry, BMI, abdominal circumference, skin-fold thickness and in-house laboratory assays for circulating lipids and biomarkers for obesity-associated disease.
Diabetes is a major disease affecting more than 400 million people globally. Like in humans, type 2 diabetes in monkeys often occurs with ageing or obesity starting from insulin resistance (IR) or impaired glucose tolerance to overt diabetes due to the failure of pancreatic β-cells. The pathogenesis and histology of β-cell failure in monkeys are particularly similar to those in humans.
The aged cynomolgus macaque has been a well-studied translational model for human atherosclerosis, hypercholesterolemia and essential hypertension when fed a cholesterol-containing diet made at KBI. Like humans, this model develops dyslipidemia and atherosclerosis in close association with obesity, diabetes and coronary arterial disease.
KBI has a large cohort of macaques with spontaneous metabolic disorders and this makes it possible to screen for well-defined models of hyperlipoproteinemia. Furthermore, the hyperlipidemia models produced by different types of high fat diets are also available for studies of the efficacy, PK/PD, biomarkers and possible adverse effects.
Cardiac magnetic resonance imaging and human-based protocols are routinely used at KBI to obtain quantitative information for:
· Lumen and vessel wall thickness
· Plaque burden and inflammation
Abdominal Aorta and Iliac Arteries