High Fat Diet, Estradiol and Retinoic Acid
Obesity is more prevalent in women (61.3 vs. 42% prevalence in men) and correlates with a higher risk for type 2 diabetes and cardiovascular disease. Fat deposition or adiposity is common before premenopause and after menopause in women who consume the Western high fat diet. Two metabolites of Vitamin A may be responsible. These metabolites retinaldehyde (Rald) and retinoicacid (RA) regulate cell differentiation and metabolism in adipose and other tissues. Low-autocrine RA generation by the cytosolic enzyme family aldehydedehydrogenase-1 (Aldh1a1, -a2, and -a3) stimulates adipogenesis -the birth of fat. It was shown that in humans, therapeutic RA doses can cause RA syndrome demonstrating increased adiposity. RA is produced primarily by visceral fat (VF) – fat that accumulates around internal organs. RA is also produced in subcutaneous fat. Both the high fat and the hormone estradiol induced Aldh1 expression in mice, possibly directly through estrogen receptor sites. The authors hypothesized that adipose tissue responds to the high fat diet and estradiol by producing RA. RA in turn increases adipogenesis or the increase in fat creation. Increases in RA generation and dysregulation of Aldh1 in mouse and human adipose are regulated by diet (high fat diet, leads to fat production) and estradiol. Experiments showed that fat cells in female mice lacking the enzyme could produce proteins that use fat for heat, meaning the fat in these females was burned away rather than stored.
These results suggest that a high fat diet and/or lack of estradiol mediate visceral fat formation through a sex-specific enzyme, the autocrine Aldh1 switch. With this switch, high fat feeding induces fat accumulation by RA instead of the usual lipolysis. Researcher saw a similar pattern in the adipose cells gathered from obese women.
Study of oleanolic acid on the estrodiol production and the fat production of mouse preadipocyte 3T3-L1 in vitro ...In conclusion, OA was found able to inhibit the fat production while maintaining the total estrogen level and the mechanisms for the above findings were preliminarily clarified, which suggests that OA may be useful to treat the menopausal obesity.