The integrated stress response is a defense system for stressed cells, and it has been clarified that it plays various roles in cells of various organs by controlling both gene expression and protein translation.However, it has not yet been clarified what role the integrated stress response plays in adipocytes that cause obesity by storing surplus energy as lipids.

　This research group investigated the effect of activating an integrated stress response in an adipocyte-specific manner using genetically modified mice.As a result, it was found that the genetically modified mice had no effect when fed with a normal diet, but the food intake decreased and the body weight gain was suppressed when fed with a high-fat diet.In addition, in the case of obesity, improvement of obesity was observed, such as a decrease in fat mass due to a decrease in eating of a high-fat feed.

　At this time, the expression of GDF15, which is known as an endocrine hormone that controls feeding behavior, is greatly increased, and the decrease in eating of high-fat feed due to the activation of integrated stress response is mediated by GDF15 and its receptor GFRAL. It was confirmed that the reaction was successful.Normally, mice preferentially eat high-fat diets, but administration of GDF15 reduced their intake of high-fat diets and began to eat regular diets.It was also found that one of the substances that activates the integrated stress response pathway in adipocytes, conjugated linoleic acid, has an action of reducing the feeding of a high-fat diet.

　Since the mechanism of feeding control by integrated stress response in adipocytes has been elucidated, this result is expected to be applied as a new therapeutic target for lifestyle-related diseases such as obesity.

Paper information:[IScience] Integrated stress response regulates GDF15 secretion from adipocytes, preferentially suppresses appetite for a high-fat diet and improves obesity