Central mechanisms of adiposity in adult female mice with androgen excess.
Obesity. 2014-02-19; 22(6): 1477-1484
DOI: 10.1002/oby.20719
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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.
Copyright © 2014 The Obesity Society.