Endocrine Abstracts

The gonadal axis is an important modulator of both energy balance and metabolism. Estradiol administration to either ovariectomized female or male rats leads to inhibition of food intake and decreased body weight. Other studies have suggested the presence of estrous cycle variation in meal size and body weight in rodents, as well as during pregnancy and lactation. Recent data also indicate that estradiol modulates the appetite responses to central and peripheral signals and that this endocrine interaction may account for important sex differences in regulation of energy balance. The general consensus assumes that most effects of estradiol on energy homeostasis are exerted at peripheral level. However, current very evidence is changing (and challenging) our perspective about the role of estrogens on energy balance from a ‘peripheral vision’ to a ‘central vision’. In this sense, recent data suggest that estrogen signalling in the ventromedial nucleus of the hypothalamus (VHM), specifically in steroidogenic factor -1, (SF1) neurons, plays a major role in the modulation of whole body energy homeostasis.

Here, we demonstrate that central administration of estradiol decreases the activity hypothalamic AMP-activated protein kinase (AMPK). Such induction of de novo lipogenesis increases activity in the sympathetic nervous system (SNS) and upregulates thermogenic markers in brown adipose tissue (BAT), leading to increased energy expenditure, and weight loss. Functional data evidence that inhibition of the lipogenic pathway in the VMH prevents CNS-mediated activation of BAT by estradiol and reverses the weight loss associated with estradiol treatment. This regulatory mechanism depends on AMPK inactivation, since genetic ablation of this enzyme in the VMH of ovariectomized rats induces feeding-independent weight loss and increased BAT thermogenesis. Overall, these findings demonstrate that estradiol-induced modulation of AMPK activity and lipid metabolism in the VMH is an important regulator of energy homeostasis.