KBI has a large colony of obese NHP models readily available for the needs of research services. We routinely evaluate anti-obese efficacy with a wide range of tools including the following techniques: · measurements of caloric intake and body mass index (BMI) · quantification of body fat composition with dual energy X-ray absorptiometry (DEXA and iDXA) · measurement of ectopic fat accumulation with magnetic resonance imaging (MRI) · molecular biomarkers (such as adipokine mRNA expression) from fat biopsy in the area of interest 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.
KBI has more than 1,000 monkeys at stages of pre-diabetes, overt diabetes and diabetes with complications for the evaluation of new drugs: · Pre-diabetes (hyperinsulinemia, impaired glucose tolerance, insulin resistance) · Type 2 diabetes with hyperinsulinemia and hypoinsulinemia · Diabetic nephropathy · Diabetic retinopathy · Diabetic Neuropathy A full array of comprehensive tools are well established for the detailed characterization at various stages including: · Clinical chemistry for metabolic profiling · Oral glucose tolerance test (OGTT), intravenous glucose tolerance test (IVGTT) and insulin tolerance test (ITT) · Oral lipid tolerance test (OLTT) and meal tolerance test (MTT) · Graded glucose infusion (GGI) · Hyperinsulinemic-euglycemic clamp · GI-bypass and gastric emptying
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 Abdominal Aorta Iliac Arteries