Vitamin A Metabolite Decreases Insulin Sensitivity and Increases Obesity

Retinaldehyde (Rald), a metabolite of vitamin A, increases the generation of adipose tissue and decreases insulin sensitivity, work conducted in a Harvard University laboratory shows. Rald inhibitors, on the other hand, decrease fat tissue and diet-induced obesity, Drs. Jorge Plutzky and Ouliana Ziouzenkova and colleagues report in an advance online publication of Nature Medicine, released May 27, 2007.

"There is a growing realization that retinoids, as naturally occurring molecules derived from vitamin A, can play important and quite specific roles in controlling gene expression," said Dr. Plutzky. "Through this, retinoids can have key roles in controlling responses, such as energy balance, obesity and diabetes. Our work is an example of this trend."

The investigators’ research showed that Rald is present in rodent fat, and that it binds to retinol-binding proteins, inhibits adipogenesis and suppresses peroxisome proliferators-activated receptor-gamma and retinoid X receptor (RXR) responses.
Investigators announced that, "Mice lacking the Rald-catabolizing enzyme retinaldehyde dehydrogenase 1 (Raldh1) resisted diet-induced obesity and insulin resistance and showed increased energy dissipation."

"Now that we know retinaldehyde may play an important role in other locations outside the eye, including in locations like fat tissue, those pathways that control retinaldehyde levels could become targets for drug therapy," Dr. Plutzky said. "Likewise, variations in genes that control retinaldehyde levels may be involved in determining factors such as body weight, obesity and diabetes.

He cautioned that the results do not suggest a need for excess vitamin A supplementation. "A balanced well-rounded diet is always a good idea. Unmonitored excessive intake of any vitamin can be associated with health issues," he warned.
Nature Medicine May 27, 2007

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