期刊
NATURE METABOLISM
卷 4, 期 7, 页码 883-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s42255-022-00587-9
关键词
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资金
- European Research Council (ERC) under the European Union [726225]
- I-CORE Gene Regulation in Complex Human Disease Center [41/11]
- Israel Science Foundation (ISF) [129/13]
- EMBO Scientific Exchange Grant [9256]
- ISF [1781/16]
- Israel Ministry of Science and Technology [3-13608, 84/19]
- EPM Inc.
- CBRC 2nd Zvi and Esther Weinstat Graduate Students 2020 award
- Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University
- European Research Council (ERC) [726225] Funding Source: European Research Council (ERC)
Ultraviolet exposure on the skin increases food intake and body weight in males, but not in females. This sexual dimorphism is mediated by the expression of ghrelin in skin adipocytes. These findings highlight the significant metabolic differences between males and females and the important role of the skin in energy homeostasis. Furthermore, this research may lead to potential sex-based treatments for endocrine-related diseases.
Ultraviolet exposure on the skin promotes food intake and body weight gain in males, but not females, by increasing ghrelin expression in skin adipocytes. 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 p53-chromatin 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.
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