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

Jan 6, 2010Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme

Estradiol helps reverse brain resistance to leptin in female mice without ovaries on a high-fat diet

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Ovariectomized mice on a high fat diet developed extreme obesity and metabolic disturbances.

Ovariectomized mice on a high fat diet exhibited extreme obesity and elevated levels of leptin and insulin compared to those on a standard diet.
Supplementation with 17beta-estradiol-3-benzoate for four weeks significantly reduced food intake and body weight in ovariectomized mice fed a standard diet.
Centrally administered leptin did not significantly affect food intake or body weight in ovariectomized mice on a high fat diet.
In contrast, leptin treatment in 17beta-estradiol-3-benzoate-supplemented ovariectomized mice on a high fat diet resulted in significant reductions in body weight.
Estrogen supplementation restored sensitivity to leptin and attenuated many metabolic syndrome parameters in ovariectomized diet-induced obese mice.
Circulating adiponectin levels were decreased following estrogen supplementation, despite stable or decreased blood sugar levels.

AI simplified

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, 17beta-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 17beta-estradiol-3-benzoate-supplemented mice. The response to centrally injected leptin in ovariectomized mice on a high fat diet was insignificant, whereas in 17beta-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 17beta-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 17beta-estradiol-3-benzoate administration in both high fat and standard diet-fed ovariectomized mice, despite of decreased or unchanged glycemia, respectively.

Full Text

Full text is available at the source.

View full text ↗

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

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief