European journal of nutritionNov 2, 2011

Estrogen reduces belly fat and helps female mice avoid obesity and poor blood sugar control

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Updated Mar 31, 2026

Abstract

Ovariectomized female mice supplemented with estrogen showed protection against obesity compared to those without supplementation.

Male mice exhibited greater susceptibility to obesity than intact female mice.
Ovariectomy in female mice removed their natural protection against obesity.
Estrogen supplementation restored protection against obesity in ovariectomized female mice.
Both male and ovariectomized female mice on a high-fat diet gained weight primarily as abdominal fat, likely due to increased fat cell size.
Male and ovariectomized female mice on a high-fat diet showed elevated leptin mRNA levels and reduced hormone-sensitive lipase mRNA compared to intact females.
The presence of estrogen significantly inhibited key fat storage-related genes in both non-ovariectomized and ovariectomized female mice receiving estrogen.

Simplified

PURPOSE: Obesity increases the risk of diabetes. The dysregulation of estrogen metabolism has been associated with the susceptibility to obesity and diabetes. Here, we explore the role estrogen plays in sex differences in obesity and glucose metabolism, specifically adipocyte biology.

METHODS: We randomized C57BL/6 J male, non-ovariectomized female, ovariectomized female, and ovariectomized female mice supplemented with 17β estradiol to receive a calorie-restricted, low- or a high-fat diet (15 mice per group). We measured weight gained, calories consumed, percent body fat, abdominal adipose tissue, adipocyte size, lipogenic and adipogenic gene expression, and glucose tolerance.

RESULTS: Male mice had a higher susceptibility to obesity than intact female mice. However, removal of the ovaries in female mice eliminated the protection to obesity and estrogen supplementation restored this protection. Male and ovariectomized female mice gained weight predominately in the form of abdominal adipose tissue possibly due to an increase in adipocyte size. Moreover, for mice consuming the high-fat diet, male and ovariectomized female mice had significantly higher levels of leptin mRNA and lower hormone-sensitive lipase mRNA relative to intact female mice and ovariectomized female mice supplemented with estrogen. Additionally, estrogen had a strong inhibitory effect on key adipogenic genes in non-ovariectomized female and ovx-female mice supplemented with estrogen. Finally, we show that male and ovariectomized female mice consuming the high-fat diet had a higher incidence of glucose intolerance.

CONCLUSION: Estrogen protects female mice from obesity and impaired glucose tolerance possibly by modulating the expression of genes regulating adipogenesis, lipogenesis, and lipolysis.

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Estrogen reduces belly fat and helps female mice avoid obesity and poor blood sugar control

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