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ANDROGEN DEFICIENCY EXACERBATES HIGH FAT DIET-INDUCED METABOLIC ALTERATIONS IN MALE MICE

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Androgen deficiency is associated with obesity, metabolic syndrome, and type 2 diabetes mellitus in men, but the mechanisms behind these associations remain unclear. In this study, we investigated the combined effects of androgen deficiency and high fat diet (HFD) on body composition and glucose homeostasis in C57BL/6J male mice. Two models of androgen deficiency were used: orchidectomy (ORX) and androgen receptor knockout (ARKO) mice. Both models displayed higher adiposity and serum leptin levels upon HFD, while no differences were seen on a regular diet. Fat accumulation in HFD ORX animals was accompanied by increased sedentary behavior and occurred in spite of reduced food intake. HFD ORX mice showed white adipocyte hypertrophy, correlated with decreased mitochondrial content but not function as well as increased lipogenesis and decreased lipolysis suggested by the upregulation of FAS and the downregulation of Lipe. Both ORX and ARKO exacerbated HFD-induced glucose intolerance by impairing insulin action in liver and skeletal muscle, as evidenced by the increased triglyceride and decreased glycogen content in these tissues. In addition, serum IL-1β levels were elevated, and pancreatic insulin secretion was impaired following ORX. Testosterone but not dihydrotestosterone supplementation restored the castration effects on body composition and glucose homeostasis. We conclude that sex steroid deficiency in combination with HFD exacerbates adiposity, insulin resistance, and beta-cell failure in two preclinical male mouse models. Our findings stress the importance of a healthy diet in a clinical context of androgen deficiency and may have implications for the prevention of metabolic alterations in hypogonadal men.
Tijdschrift: Endocrinology
ISSN: 0013-7227
Issue: 2
Volume: 157
Pagina's: 648 - 65
Jaar van publicatie:2016
BOF-keylabel:ja
IOF-keylabel:ja
BOF-publication weight:1
CSS-citation score:2
Authors from:Higher Education
Toegankelijkheid:Closed