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Vitamin A Metabolite Linked to Sex-Specific Fat Accumulation

Aldehyde dehydrogenase 1 may explain why women accumulate abdominal fat

WEDNESDAY, Sept. 12 (HealthDay News) -- An enzyme that regulates the levels of a vitamin A metabolite may play a role in explaining why women are more prone to obesity and accumulation of abdominal fat, particularly after menopause, according to a study published online Aug. 28 in Diabetes.

Noting that the prevalence of obesity is higher in women, and that retinoic acid can stimulate adipogenesis, Rumana Yasmeen, from The Ohio State University in Columbus, and colleagues investigated the role of aldehyde dehydrogenase 1 (Aldh1a1, -a2, and -a3), the major enzymes that generate retinoic acid, in sex-specific fat deposition.

The researchers found that, in mice lacking one variant of Aldh1 (Aldh1a1−/−), only female mice became resistant to visceral adipose formation after being fed a high-fat diet. This was due to increased expression of adipose triglyceride lipase, an enzyme that breaks down fat, which was noted in female but not male Aldh1a1−/− mice. Estrogen was found to reduce Aldh1a3 expression, attenuating conversion of retinaldehyde to retinoic acid, while ovariectomized mice had significantly increased Aldh1a3 expression. Aldh1 enzymes were expressed at higher levels in stromal cells isolated from visceral fat from obese humans compared with lean humans.

"Our data suggest that a high-fat diet and/or lack of estrogen mediates visceral fat formation through a sex-specific autocrine Aldh1 switch, in which lipolysis, mediated by an induction of adipose triglyceride lipase through retinaldehyde, is replaced by retinoic acid-mediated lipid accumulation," Yasmeen and colleagues conclude.

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