Ultraviolet exposure on the skin promotes food intake and body weight gain in males, but not females, by increasing ghrelin expression in skin adipocytes.
(2022)Cite this article
Sexual dimorphisms are responsible for profound metabolic differences in health and behavior. Whether males and females react differently to environmental cues, such as solar ultraviolet (UV) exposure, is unknown. Here we show that solar exposure induces food-seeking behavior, food intake, and food-seeking behavior and food intake in men, but not in women, through epidemiological evidence of approximately 3,000 individuals throughout the year. In mice, UVB exposure leads to increased food-seeking behavior, food intake and weight gain, with a sexual dimorphism towards males. In both mice and human males, increased appetite is correlated with elevated levels of circulating ghrelin. Specifically, UVB irradiation leads to p53 transcriptional activation of ghrelin in skin adipocytes, while a conditional p53-knockout in mice abolishes UVB-induced ghrelin expression and food-seeking behavior. In females, estrogen interferes with the p53âchromatin interaction on the ghrelin promoter, thus blocking ghrelin and food-seeking behavior in response to UVB exposure. These results identify the skin as a major mediator of energy homeostasis and may lead to therapeutic opportunities for sex-based treatments of endocrine-related diseases.
Sex differences have profound effects on health and behavior1. Yet, whether men and women react differently to environmental cues, such as ultraviolet (UV) radiation, remains under investigated. UV was recognized as a carcinogen in 1928 (ref. 2), sparking a massive cultural trend of minimizing exposure to the sun from the mid-1900s2. But subsequent epidemiological studies have painted a more complex picture of UVâs role in human health, by indicating that it can extend life expectancy, due to protection against cardiovascular disease and other causes of mortality2. Sun exposure increase liver metabolism, protecting the organ from hepatocellular lipotoxicity3 and metabolic disease3.
The solar radiationâs health benefits have been attributed to vitamin D4. But two recent large-scale clinical trials showed that vitamin D alone was not associated with reduced risk of cardiovascular disease, all-cause mortality and invasive cancer4. These findings indicate that at least some of the health benefits of sunlight are independent of vitamin D.