Estrogen restores brain insulin sensitivity in ovariectomized non-obese rats, but not in ovariectomized obese rats

Apr 19, 2014Metabolism: clinical and experimental

Estrogen improves brain insulin response in non-obese rats without ovaries but not in obese rats without ovaries

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Abstract

Ovariectomized rats on a high-fat diet showed reduced brain insulin sensitivity and increased brain oxidative stress that were not improved by estrogen treatment.

Ovariectomy and a high-fat diet led to obesity and decreased insulin sensitivity in both peripheral and brain tissues.
Increased brain oxidative stress was observed in ovariectomized rats and those on a high-fat diet.
Estrogen treatment improved peripheral insulin sensitivity in ovariectomized rats but had no effect on brain insulin sensitivity in those on a high-fat diet.
Estrogen was effective in reversing brain insulin sensitivity and oxidative stress only in ovariectomized rats fed a normal diet.

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OBJECTIVE: We previously demonstrated that obesity caused the reduction of peripheral and brain insulin sensitivity and that estrogen therapy improved these defects. However, the beneficial effect of estrogen on brain insulin sensitivity and oxidative stress in either ovariectomy alone or ovariectomy with obesity models has not been determined. We hypothesized that ovariectomy alone or ovariectomy with obesity reduces brain insulin sensitivity and increases brain oxidative stress, which are reversed by estrogen treatment.

MATERIALS/METHODS: Thirty female rats were assigned as either sham-operated or ovariectomized. After the surgery, each group was fed either a normal diet or high-fat diet for 12 weeks. At week 13, rats in each group received either the vehicle or estradiol for 30 days. At week 16, blood and brain were collected for determining the peripheral and brain insulin sensitivity as well as brain oxidative stress.

RESULTS: We found that ovariectomized rats and high-fat diet fed rats incurred obesity, reduced peripheral and brain insulin sensitivity, and increased brain oxidative stress. Estrogen ameliorated peripheral insulin sensitivity in these rats. However, the beneficial effect of estrogen on brain insulin sensitivity and brain oxidative stress was observed only in ovariectomized normal diet-fed rats, but not in ovariectomized high fat diet-fed rats.

CONCLUSIONS: Our results suggested that reduced brain insulin sensitivity and increased brain oxidative stress occurred after either ovariectomy or obesity. However, the reduced brain insulin sensitivity and the increased brain oxidative stress in ovariectomy with obesity could not be ameliorated by estrogen treatment.

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Estrogen restores brain insulin sensitivity in ovariectomized non-obese rats, but not in ovariectomized obese rats

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