Use and Importance of Nonhuman Primates in Metabolic Disease Research: Current State of the Field

Abstract

Obesity and its multiple metabolic sequelae, including type 2 diabetes, cardiovascular disease, and fatty liver disease, are becoming increasingly widespread in both the developed and developing world. There is an urgent need to identify new approaches for the prevention and treatment of these costly and prevalent metabolic conditions. Accomplishing this will require the use of appropriate animal models for preclinical and translational investigations in metabolic disease research. Although studies in rodent models are often useful for target/pathway identification and testing hypotheses, there are important differences in metabolic physiology between rodents and primates, and experimental findings in rodent models have often failed to be successfully translated into new, clinically useful therapeutic modalities in humans. Nonhuman primates represent a valuable and physiologically relevant model that serve as a critical translational bridge between basic studies performed in rodent models and clinical studies in humans. The purpose of this review is to evaluate the evidence, including a number of specific examples, in support of the use of nonhuman primate models in metabolic disease research, as well as some of the disadvantages and limitations involved in the use of nonhuman primates. The evidence taken as a whole indicates that nonhuman primates are and will remain an indispensable resource for evaluating the efficacy and safety of novel therapeutic strategies targeting clinically important metabolic diseases, including dyslipidemia and atherosclerosis, type 2 diabetes, hepatic steatosis, steatohepatitis, and hepatic fibrosis, and potentially the cognitive decline and dementia associated with metabolic dysfunction, prior to taking these therapies into clinical trials in humans.

Fructose-induced hypertriglyceridemia in rhesus macaques is attenuated with fish oil or ApoC3 RNA interference

“…Nonhuman primates have a number of clear advantages over more commonly used rodent models of metabolic disease. They are more closely related evolutionarily and have metabolic physiology and lipid metabolism that are more similar to that in humans (18,19). Rhesus macaques provided with fructose-sweetened beverages rapidly develop insulin resistance, hypertriglyceridemia, and inflammation (17).…”

Estradiol treatment in a nonhuman primate model of menopause preserves affective reactivity

“…Middle-aged monkeys and aged surgically menopausal monkeys on estradiol treatment showed the same patterns that have been widely documented: as threat levels increase, so too does affective responding. Despite wide interest in human healthy affective aging, animal studies have primarily paid attention to cognition (for reviews Baxter, 2001;Voytko & Tinkler, 2004) and disease models (for reviews (Colman, 2017;Havel, Kievit, Comuzzie, & Bremer, 2017) . Only very recently have nonhuman primates' affective processes been considered in the context of aging (Almeling, Hammerschmidt, Sennhenn-Reulen, Freund, & Fischer, 2016;Weiss, King, Inuoue-Murayama, Matsuzawa, & Oswald, 2012).…”

Nicotine in Senescence and Atherosclerosis

“…Murine models are most commonly used for nicotine and tobacco studies [70][71][72][73][74], although other animal models, including primates and C. elegans, have been used for behavioral and metabolic studies [75][76][77]. Species differences exist in nicotine metabolism, and non-human primates metabolize nicotine in a similar manner to humans [78]. In humans, while the tissue half-life of nicotine after smoking a cigarette is only about 8 min, the plasma half-life is 2 h. Metabolites of nicotine have a longer half-life.…”