Food-seeking behavior is triggered by skin ultraviolet exposure in males

Shivang Parikh, Roma Parikh, Keren Michael, Lior Bikovski, Georgina Barnabas, Mariya Mardamshina, Rina Hemi, Paulee Manich, Nir Goldstein, Hagar Malcov-Brog, Tom Ben-Dov, Ohad Glaich, Daphna Liber, Yael Bornstein, Koral Goltseker, Roy Ben-Bezalel, Mor Pavlovsky, Tamar Golan, Liron Spitzer, Hagit MatzPinchas Gonen, Ruth Percik, Lior Leibou, Tomer Perluk, Gil Ast, Jacob Frand, Ronen Brenner, Tamar Ziv, Mehdi Khaled, Shamgar Ben-Eliyahu, Segev Barak, Orit Karnieli-Miller, Eran Levin, Yftach Gepner, Ram Weiss, Paul Pfluger, Aron Weller, Carmit Levy*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)883-900
Number of pages18
JournalNature Metabolism
Volume4
Issue number7
DOIs
StatePublished - Jul 2022

Funding

FundersFunder number
Department of Human Genetics and Biochemistry
EPM Inc.
I-CORE Gene Regulation in Complex Human Disease Center41/11
European Molecular Biology Organization9256, 1781/16
Horizon 2020 Framework Programme726225
Kurume University
European Research Council
Israel Science Foundation129/13
Tel Aviv University
Ministry of Science and Technology, Israel3-13608, 84/19
Universität Ulm
Sackler Faculty of Medicine, Tel-Aviv University

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