Central mechanisms of adiposity in adult female mice with androgen excess

Obesity (Silver Spring). 2014 Jun;22(6):1477-84. doi: 10.1002/oby.20719. Epub 2014 Feb 19.

Abstract

Objective: Androgen excess in women is associated with visceral adiposity. However, little is known on the mechanism through which androgen promotes visceral fat accumulation.

Methods: To address this issue, female mice to chronic androgen excess using 5α-dihydrotestosterone (DHT) and studied the regulation of energy homeostasis was exposed.

Results: DHT induced a leptin failure to decrease body weight associated with visceral adiposity but without alterations in leptin anorectic action. This paralleled leptin's failure to upregulate brown adipose tissue expression of uncoupling protein-1, associated with decreased energy expenditure (EE). DHT decreased hypothalamic proopiomelanocortin (pomc) mRNA expression and increased POMC intensity in neuronal bodies of the arcuate nucleus while simultaneously decreasing the intensity of POMC projections to the dorsomedial hypothalamus (DMH). This was associated with a failure of the melanocortin 4 receptor agonist melanotan-II to suppress body weight.

Conclusion: Taken together, these data indicate that androgen excess promotes visceral adiposity with reduced POMC neuronal innervation in the DMH, reduced EE but without hyperphagia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, Brown / drug effects
  • Adipose Tissue, Brown / metabolism
  • Adiposity / physiology*
  • Androgens / administration & dosage*
  • Androgens / adverse effects
  • Androgens / blood*
  • Animals
  • Arcuate Nucleus of Hypothalamus / drug effects
  • Arcuate Nucleus of Hypothalamus / metabolism
  • Body Composition
  • Body Weight
  • Dihydrotestosterone / administration & dosage*
  • Dihydrotestosterone / blood*
  • Energy Metabolism
  • Female
  • Hyperphagia / pathology
  • Hypothalamus / drug effects
  • Hypothalamus / metabolism
  • Intra-Abdominal Fat / drug effects*
  • Intra-Abdominal Fat / metabolism
  • Ion Channels / genetics
  • Ion Channels / metabolism
  • Leptin / blood
  • Mice
  • Mice, Inbred C57BL
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Obesity / metabolism
  • Peptides, Cyclic / metabolism
  • Pro-Opiomelanocortin / genetics
  • Pro-Opiomelanocortin / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptor, Melanocortin, Type 4 / genetics
  • Receptor, Melanocortin, Type 4 / metabolism
  • Uncoupling Protein 1
  • Up-Regulation
  • alpha-MSH / analogs & derivatives
  • alpha-MSH / metabolism

Substances

  • Androgens
  • Ion Channels
  • Leptin
  • MC4R protein, mouse
  • Mitochondrial Proteins
  • Peptides, Cyclic
  • RNA, Messenger
  • Receptor, Melanocortin, Type 4
  • Ucp1 protein, mouse
  • Uncoupling Protein 1
  • Dihydrotestosterone
  • melanotan-II
  • alpha-MSH
  • Pro-Opiomelanocortin