Fructose-fed rhesus monkeys: a nonhuman primate model of insulin resistance, metabolic syndrome, and type 2 diabetes

Abstract

The incidence of insulin resistance has increased dramatically over the past several years, and we and others have proposed that this increase may at least in part be attributable to increased dietary fructose consumption. However, a major limitation to the study of diet-induced insulin resistance is the lack of relevant animal models. Numerous studies, mostly in rodents, have demonstrated that diets high in fructose induce insulin resistance; however, important metabolic differences exist between rodents and primates. Thus, the results of metabolic studies performed in primates are substantively more translatable to human physiology, underscoring the importance of establishing nonhuman primate models of common metabolic conditions. In this report, we demonstrate that a high-fructose diet in rhesus monkeys produces insulin resistance and many features of the metabolic syndrome, including central obesity, dyslipidemia, and inflammation within a short period of time; moreover, a subset of monkeys developed type 2 diabetes. Given the rapidity with which the metabolic changes occur, and the ability to control for many factors that cannot be controlled for in humans, fructose feeding in rhesus monkeys represents a practical and efficient model system in which to investigate the pathogenesis, prevention, and treatment of diet-induced insulin resistance and its related comorbidities.

Figure 1

The effect of a high‐fructose diet on (A) body weight, (B) fat mass, (C) energy intake, and (D) energy expenditure in rhesus monkeys with diet‐induced metabolic syndrome. *p≤ 0.05, **p≤ 0.01, ***p≤ 0.001 versus baseline by linear mixed model. Error bars show SEM.

Figure 2

The glucose (A) and insulin (B) responses during intravenous glucose tolerance testing in rhesus monkeys with diet‐induced metabolic syndrome, and the glucose (C) and insulin (D) responses during intravenous glucose tolerance testing in rhesus monkeys with diet‐induced diabetes. Error bars show SEM.