Endocrine Abstracts

Low-carbohydrate/high fat diets (LC-HFD) effectively induce body weight loss in both animals and humans; however, in rats this is paralleled by increased visceral adiposity contributing to impaired glucose tolerance. Estrogen inhibits adipose tissue accumulation, with estrogen deficient female animals displaying increased body weight and visceral adiposity with reduced insulin sensitivity, which can be reversed with estrogen replacement. Consistent with the effects seen in females, estrogen supplementation also improves insulin sensitivity in male animals. Within the hypothalamus, the arcuate nucleus (ARC) is a key area of metabolic control. To test the hypothesis that central estrogen signalling plays a role for the phenotype observed with LC-HFD in rats, we investigated whether pair-feeding isoenergetic amounts of two different LC-HFD affects estrogen receptor alpha (ERα) expression in the ARC. Male Wistar rats (12-week old) were isoenergetically pair-fed on chow (CH), ‘Atkins-style’ LC-HFD1, (protein matched to chow, 78.7/19.1/2.2); and ketogenic LC-HFD2 (low protein content, 92.8/5.5/1.7) (% of metabolisable energy, fat/protein/carbohydrate) for 4 weeks. Rats were perfused with 4% paraformaldehyde and excised brains were cryosectioned at 30 μm and immunohistochemistry was used to visualize ERα expression. Overall, ERα was selectively expressed in the ARC. When comparing the different diet groups, immunohistochemistry revealed a decreased expression of ERα in the ARC of both LC-HFD1 and LC-HFD2 when compared to CH rats. There was no difference between LC-HFD1 and LC-HFD2. In conclusion, due to the fundamental role of estrogen in the control of adiposity and insulin sensitivity, our findings suggest that central expression of ERα is regulated by the macronutrient composition of a diet. Furthermore, the phenotype observed with LC-HFD may be related to decreased ERα expression in the ARC.