A high-fat diet increases body weight and circulating estradiol levels but does not improve bone structural properties in ovariectomized mice

Authors: Cao, Jay; Gregoire, Brian

Submitted to: Nutrition Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/10/2015
Publication Date: 4/1/2016
Publication URL: https://handle.nal.usda.gov/10113/62805
Citation: Cao, J.J., Gregoire, B.R. 2016. A high-fat diet increases body weight and circulating estradiol levels but does not improve bone structural properties in ovariectomized mice. Nutrition Research. 36(4):320-327.

Interpretive Summary: Estrogen deficiency induces a significant bone loss by increasing bone resorption in humans and animals. Adipose tissue has been considered an important source of estrogen when the ovary ceases producing estrogen. We investigated whether the effect of diet-induced obesity on circulating estrogen and bone structure in an estrogen deficient animal model. Thirty-six female C57BL/6 mice were either ovariectomized or sham-operated at 4-mo-old and were fed either a normal-fat (10% energy as fat) or a high-fat (45% energy as fat) diet ad libitum for 12 wks. We demonstrate that Ovariectomy resulted in estrogen deficiency and bone loss with body weight gain. A high-fat diet increased circulating estrogen in ovariectomized mice but did not improve bone structural parameters compared to mice fed a normal-fat diet. Our results indicate that estrogen deficient mice are more susceptible to obesity in response to a high-fat diet and increased circulating estrogen due to the high-fat diet does not protect ovariectomy-induced bone loss.

Technical Abstract: Ovariectomy-induced estrogen deficiency increases adiposity and induces substantial bone loss by increasing osteoclast activity. Diet-induced obesity is detrimental to bone mass by increasing bone resorption in various animal models. This study investigated whether obesity induced by a high-fat diet alter circulating estradiol levels, mitigates or exacerbates bone structure deterioration, and changes markers of bone resorption and formation in ovariectomized mice. We hypothesized that a high-fat diet-induced obesity exacerbates bone loss caused by ovariectomy. Thirty-six female C57BL/6 mice at 4-mo-old were either sham-operated or ovariectomized and fed either a normal-fat diet (10% kcal as fat) or a high-fat diet (45% kcal as fat with extra fat from lard) ad libitum for 12 wks. Ovariectomy resulted in increased body weight, serum tartrate-resistant acid phosphatase level, and expression of cathepsin K in bone; decreased serum estradiol level; and induced significant bone loss by decreasing BV/TV, Conn.D, Tb.N, and Tb.Th while increasing Tb.Sp and SMI (P < 0.05). High-fat diet increased body weight in ovariectomized mice and slightly decreased BV/TV (P = 0.08) and SMI (P = 0.09) compared to normal-fat diet feeding. Despite having similar serum estradiol levels and higher body weight, ovariectomized mice consuming the high-fat diet had lower BV/TV, Conn.D, Tb.N, Tb.Th and greater SMI and Tb.Sp than sham mice fed the normal-fat diet. These findings indicate that increased body weight and serum estradiol in ovariectomized mice in response to a high-fat diet does not protect ovariectomy-induced bone loss.