Oral Presentation The International Congress of Neuroendocrinology 2014

Estradiol prevents fat accumulation and restores leptin sensitivity in high fat diet fed mice (#119)

Sara A Litwak 1 , Jenny L Wilson 1 , Weiyi Chen 1 , Mohammad Khaksary 2 , Michael A Cowley 1 , Pablo J Enriori 1
  1. Physiology, Monash University, Clayton, Victoria, Australia
  2. Physiology, Kerman University of Medical Sciences, Kerman, Iran

In pre-menopausal and menopausal women in particular, suboptimal estrogens have been linked to the development of the metabolic syndrome as major contributors to fat accumulation. At the same time, estrogen has been described to have a role in regulating body metabolic status. In this work we evaluated how endogenous or administered estrogens impact on the changes associated with high fat diet (HFD) consumption in two different paradigms; ovarian-intact and in ovariectomized (OVX) mice.

When estradiol (E2) was cyclically administered to ovarian-intact HFD fed mice for twelve weeks, animals gained significantly less weight than ovarian-intact vehicle controls (p<0.01). This difference was mainly due to a reduced caloric intake but not to an increase in energy expenditure (EE) or locomotor activity (LA). This E2 treatment regime to mice exposed to HFD lead to visceral fat content to the same levels as in mice fed a regular chow diet. In the ovarectomized model, the main body weight and fat content reducing action of E2 was not only through decreasing food intake, but also by increasing whole body EE, LA and by inducing fat oxidation. Importantly, these animals became responsive to the anorexigenic effects of (intraventricularly administered) leptin in contrast to the vehicle treated and to the pair fed control groups (p<0.01). Further in vitro hypothalamic secretion experiments revealed that treatment of obese mice with E2 is able to modulate the secretion of appetite regulating neuropeptides; namely, to increase the secretion of the anorectic neuropeptide α-MSH (p<0.01) and decrease the secretion of the orexigenic neuropetides NPY and AgRP (p<0.01 and p<0.05 respectively).  

In conclusion, differences in response to E2 treatment of HFD fed animals depend on their endogenous estrogenic status. Overall, E2 administration overcomes arcuate leptin resistance and partially prevents fat accumulation on these mice.