Journal
HORMONE AND METABOLIC RESEARCH
Volume 42, Issue 3, Pages 182-186Publisher
GEORG THIEME VERLAG KG
DOI: 10.1055/s-0029-1243250
Keywords
leptin; estrogen deficiency; obesity; adipokines
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Funding
- Grant Agency of the Czech Republic [305/06/0427, 303/09/0744]
- Academy of Sciences of the Czech Republic [Z40550506]
- Ministry of Health of the Czech Republic [MZOVFN2005]
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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, 17 beta-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 17 beta-estradiol-3-benzoate supplemented mice. The response to centrally injected leptin in ovariectomized mice on a high fat diet was insignificant, whereas in 17 beta-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 17 beta-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 17 beta-estradiol-3-benzoate administration in both high fat and standard dietfed ovariectomized mice, despite of decreased or unchanged glycemia, respectively.
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