Estradiol Supplementation Helps Overcome Central Leptin Resistance of Ovariectomized Mice on a High Fat Diet

Abstract

Ovariectomized mice on a high fat diet represent a model of diet-induced obesity during estrogen deficiency. Here, we tested the hypothesis that sensitivity to centrally administered leptin in ovariectomized mice with diet-induced obesity could be restored by estrogen supplementation. Ovariectomized C57BL/6 female mice were fed either a standard or high fat diet until they were 27 weeks old. Ovariectomized mice on a high fat diet developed extreme obesity and hyperleptinemia and moderate hyperinsulinemia compared to those on a standard diet. For the last 4 weeks, 17β-estradiol-3-benzoate or its vehicle was administered subcutaneously in a 4-day cyclic regimen. Finally, leptin or saline was injected into the third ventricle, and food intake and body weight were measured for 36 h. In ovariectomized mice fed a standard diet, the decrease in food intake and body weight was significant and was pronounced in 17β-estradiol-3-benzoate-supplemented mice. The response to centrally injected leptin in ovariectomized mice on a high fat diet was insignificant, whereas in 17β-estradiol-3-benzoate-supplemented mice, the effect was significant, particularly with respect to body weight. We showed for the first time that central insensitivity to leptin in ovariectomized diet-induced obese mice was restored with 17β-estradiol-3-benzoate supplementation, which also attenuated most of the parameters of metabolic syndrome. Only circulating adiponectin, a peripheral insulin sensitivity marker, was lowered following 17β-estradiol-3-benzoate administration in both high fat and standard diet-fed ovariectomized mice, despite of decreased or unchanged glycemia, respectively.

leptin - estrogen deficiency - obesity - adipokines

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Notice: The text was changed in accordance with the erratum by January 21th, 2010. In Table 1 of the original article the values for triglycerides (mg/dl) are incorrect. The correct values are: 58.2, 66.1, 70.7 and 68.8 mg/dl

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