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Androgen deficiency exacerbates high-fat diet-induced metabolic alterations in male mice

(2016) ENDOCRINOLOGY. 157(2). p.648-665
Author
Organization
Abstract
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 mice. Both models displayed higher adiposity and serum leptin levels upon HFD, whereas 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 up-regulation of fatty acid synthase and the down-regulation of hormone-sensitive lipase. Both ORX and androgen receptor knockout 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-1 beta levels were elevated, and pancreatic insulin secretion was impaired after 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 2 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.
Keywords
INSULIN-RESISTANCE, DEPRIVATION THERAPY, PLASMA ADIPONECTIN, HEPATIC, STEATOSIS, ADIPOSE-TISSUE, RAT MODEL, TESTOSTERONE, RECEPTOR, MEN, KNOCKOUT

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MLA
Dubois, Vanessa, et al. “Androgen Deficiency Exacerbates High-Fat Diet-Induced Metabolic Alterations in Male Mice.” ENDOCRINOLOGY, vol. 157, no. 2, 2016, pp. 648–65, doi:10.1210/en.2015-1713.
APA
Dubois, V., Laurent, M. R., Jardi, F., Antonio, L., Lemaire, K., Goyvaerts, L., … Claessens, F. (2016). Androgen deficiency exacerbates high-fat diet-induced metabolic alterations in male mice. ENDOCRINOLOGY, 157(2), 648–665. https://doi.org/10.1210/en.2015-1713
Chicago author-date
Dubois, Vanessa, Michael R. Laurent, Ferran Jardi, Leen Antonio, Katleen Lemaire, Lotte Goyvaerts, Louise Deldicque, et al. 2016. “Androgen Deficiency Exacerbates High-Fat Diet-Induced Metabolic Alterations in Male Mice.” ENDOCRINOLOGY 157 (2): 648–65. https://doi.org/10.1210/en.2015-1713.
Chicago author-date (all authors)
Dubois, Vanessa, Michael R. Laurent, Ferran Jardi, Leen Antonio, Katleen Lemaire, Lotte Goyvaerts, Louise Deldicque, Geert Carmeliet, Brigitte Decallonne, Dirk Vanderschueren, and Frank Claessens. 2016. “Androgen Deficiency Exacerbates High-Fat Diet-Induced Metabolic Alterations in Male Mice.” ENDOCRINOLOGY 157 (2): 648–665. doi:10.1210/en.2015-1713.
Vancouver
1.
Dubois V, Laurent MR, Jardi F, Antonio L, Lemaire K, Goyvaerts L, et al. Androgen deficiency exacerbates high-fat diet-induced metabolic alterations in male mice. ENDOCRINOLOGY. 2016;157(2):648–65.
IEEE
[1]
V. Dubois et al., “Androgen deficiency exacerbates high-fat diet-induced metabolic alterations in male mice,” ENDOCRINOLOGY, vol. 157, no. 2, pp. 648–665, 2016.
@article{8737867,
  abstract     = {{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 mice. Both models displayed higher adiposity and serum leptin levels upon HFD, whereas 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 up-regulation of fatty acid synthase and the down-regulation of hormone-sensitive lipase. Both ORX and androgen receptor knockout 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-1 beta levels were elevated, and pancreatic insulin secretion was impaired after 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 2 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.}},
  author       = {{Dubois, Vanessa and Laurent, Michael R. and Jardi, Ferran and Antonio, Leen and Lemaire, Katleen and Goyvaerts, Lotte and Deldicque, Louise and Carmeliet, Geert and Decallonne, Brigitte and Vanderschueren, Dirk and Claessens, Frank}},
  issn         = {{0013-7227}},
  journal      = {{ENDOCRINOLOGY}},
  keywords     = {{INSULIN-RESISTANCE,DEPRIVATION THERAPY,PLASMA ADIPONECTIN,HEPATIC,STEATOSIS,ADIPOSE-TISSUE,RAT MODEL,TESTOSTERONE,RECEPTOR,MEN,KNOCKOUT}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{648--665}},
  title        = {{Androgen deficiency exacerbates high-fat diet-induced metabolic alterations in male mice}},
  url          = {{http://dx.doi.org/10.1210/en.2015-1713}},
  volume       = {{157}},
  year         = {{2016}},
}

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