Sex Differences in Androgen Regulation of Metabolism in Nonhuman Primates

Abstract

The in-depth characterization of sex differences relevant to human physiology requires the judicious use of a variety of animal models and human clinical data. Nonhuman primates (NHPs) represent an important experimental system that bridges rodent studies and clinical investigations. NHP studies have been especially useful in understanding the role of sex hormones in development and metabolism and also allow the elucidation of the effects of pertinent dietary influences on physiology pertinent to disease states such as obesity and diabetes. This chapter summarizes the current state of our understanding of androgen effects on male and female NHP metabolism relevant to hypogonadism in human males and polycystic ovary syndrome in human females, as well as the interaction between altered androgen levels and dietary restriction and excess, in particular the western-style diet that underlies significant human pathophysiology.

Naturally Occurring and Experimentally Induced Rhesus Macaque Models for Polycystic Ovary Syndrome: Translational Gateways to Clinical Application

“…In peripubertal T onset females, diminished basal lipolysis in both SC and visceral abdominal fat depots co-occurs with augmented insulin-mediated FFA uptake into visceral adipocytes, alone, contributing to enlarged visceral, but not SC, adipocytes [162]. Since adrenergic (sympathetic nervous system noradrenalin) stimulation of lipolysis is also diminished only in SC adipocytes, unaffected adrenergic stimulation of lipolysis in enlarged visceral adipocytes likely contributes increased lipid release into the liver, with subsequent adiposity-associated insulin resistance and compensatory hyperinsulinemia [162]. T + WSD female macaques thus demonstrate the need for the onset of both hyperandrogenism and high fat diet during adolescence to evoke the adult metabolic derangements engaged by early-to-mid gestation T exposure, alone (models #8 vs. #3, respectively, Figure 1).…”

“…Partially emulating the metabolic outcomes of early-to-mid gestation T-exposure, female macaques exposed to peripubertal onset of T, and supplemented with a high fat diet (T + WSD), demonstrate increased abdominal 'android' fat and abdominal circumference indicative of increased visceral adiposity [132]. In peripubertal T onset females, diminished basal lipolysis in both SC and visceral abdominal fat depots co-occurs with augmented insulin-mediated FFA uptake into visceral adipocytes, alone, contributing to enlarged visceral, but not SC, adipocytes [162]. Since adrenergic (sympathetic nervous system noradrenalin) stimulation of lipolysis is also diminished only in SC adipocytes, unaffected adrenergic stimulation of lipolysis in enlarged visceral adipocytes likely contributes increased lipid release into the liver, with subsequent adiposity-associated insulin resistance and compensatory hyperinsulinemia [162].…”

“…T + WSD female macaques thus demonstrate the need for the onset of both hyperandrogenism and high fat diet during adolescence to evoke the adult metabolic derangements engaged by early-to-mid gestation T exposure, alone (models #8 vs. #3, respectively, Figure 1). Female macaques receiving peripubertal T onset without high fat supplementation do not exhibit such metabolic dysfunction and weight gain [132,162]. Since blood lipid levels, pancreatic beta cell defects and diminished adipocyte size are not reported, it can only be speculated that neither adipogenic constraint nor lipotoxicity become a pathological consequence when female macaques are exposed to peripubertal onset of hyperandrogenism, alone.…”

Short-Term Caloric Restriction Attenuates Obesity-Induced Pro-inflammatory Response in Male Rhesus Macaques

“…In summary, the present study advances our understanding of the functional and transcriptional response in SC-WAT associated with dynamic changes in fat mass in response to diet-induced obesity and weight loss and expands our previous studies in NHPs [17,18,20,[64][65][66]. Our study has several limitations.…”

Sex differences in the effects of high-fat diet on mouse sciatic nerves

“…Sex hormones, such as estrogen and androgen, contribute to the sex differences in body weight and metabolism between males and females and are thought to be responsible for sex-specific differences (Ogawa et al, 2015;Boese et al, 2017;True et al, 2017). Multiple studies have shown that estrogen prevented cell death in many cell types (Kanda and Watanabe, 2003;Kim et al, 2006;Vasconsuelo et al, 2008;Bailey et al, 2012).…”