Role of estrogen in hypoglycemia- and glucoprivation-induced food intake

 

Akira Takamata, Kana Miyake, and Keiko Morimoto

Department of Environmental Health, Nara Women's University, Nara, 630-8506, Japan

 

Maintenance of a desirable weight is important to reduce risks for lifestyle-related diseases, such as cerebro- and cardiovascular diseases and diabetics. Incidence of obesity and lifestyle-related diseases reportedly increase in postmenopausal women with aging, suggesting that female gonadal hormones play an important role in energy balance. Body weight is regulated by both energy intake and expenditure, and estrogen has an anorexic action. Thus, to elucidate the mechanism for estrogen-induced anorexia, we examined the effect of estrogen (E2) replacement in ovariectomized rats on food intake and lateral hypothalamic orexinergic neuron’s activity during glucoprivation induced by i.v. 2-deoxy-D-glucose (2DG) administration and hypoglycemia induced by s.c. insulin administration. Rats were ovariectomized and implanted a silicon capsule containing E2 or vehicle (cholesterol) subcutaneously. Two weeks after the replacement, rats were injected with either 2DG (400 mg/kg) or insulin (5 units/kg), and food intake was measured for 3-4 hours. The same experiment was performed for immunohistochemical examination of c-Fos and orexin A expressions in the lateral hypothalamic area (LH) and c-Fos at the arcuate nucleus (Arc). Both 2DG and insulin administration induced c-Fos expression in the orexin A neurons locating at the perifornical region of LH, and significantly induced food intake. Both 2DG- and insulin-induced food intakes were significantly lower in E2-replaced group than E2-deficit group. The fraction of c-Fos expressed orexinergic neurons, induced by both 2DG and insulin injections, were significantly less in E2-replaced group than E2-deficit group. The number of c-Fos ir cells was less in Arc in E2-replaced than E2-deficit rats. The attenuation of food intake and neuronal activation by E2 replacement was larger when rats were stimulated by insulin than by 2DG. These data indicate that E2-replacement attenuates food intake induced by 2DG and insulin possibly via the reduced neuronal activities of perifornical orexinergic and Arc neurons. Our results also suggest that E2 deficit also reduce central anorexic effect of insulin.

 

Key words: estrogen, lateral hypothalamic area, orexin, food intake, energy balance