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

Research output: Contribution to journalArticlepeer-review

20 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

Bibliographical note

Publisher Copyright:
© 2022, The Author(s).

Funding

The authors gratefully thank Professor Masayasu Kojima (Kurume University, Japan) for the gift of the ghrelin promoter plasmid, Professor Moshe Oren (Weizmann Institute, Israel) for the gift of the p53 plasmids, useful discussions and reviewing the paper, Professor Jason Caroll (University of Cambridge, UK) for the gift of the ER-α plasmid, Professor Eli Pikarsky (The Hebrew University of Jerusalem, Israel) for the gift of the p53-floxed mice and Professor Peter Moeller (University of Ulm, Germany) for the gift of the LiSa-2 cells. C.L. gratefully thanks Professor Noga Kronfeld-Schor (Tel Aviv University, Israel) for useful discussions. C.L. acknowledges grant support from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programmer (grant agreement no. 726225), the I-CORE Gene Regulation in Complex Human Disease Center (no. 41/11) and Israel Science Foundation (ISF) (grant 129/13). C.L. thanks Yuval and Omer Levy for exponential joy and Medina and Elisha Levy for tremendous support. S.P. is the recipient of a 2017 I-core travel scholarship, 4thDjerassi graduate student symposium 2019 award, 2020 student excellence award at the Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, CBRC 2ndZvi and Esther Weinstat Graduate Students 2020 award and EMBO Scientific Exchange Grant (no. 9256). S.P. thanks Smita Sunil Parikh and Rushita Parikh for the journey. Parts of the research in A.W.’s lab is supported by the ISF (grant 1781/16), Israel Ministry of Science and Technology (grants 3-13608 and 84/19) and EPM Inc. The authors gratefully thank Professor Masayasu Kojima (Kurume University, Japan) for the gift of the ghrelin promoter plasmid, Professor Moshe Oren (Weizmann Institute, Israel) for the gift of the p53 plasmids, useful discussions and reviewing the paper, Professor Jason Caroll (University of Cambridge, UK) for the gift of the ER-α plasmid, Professor Eli Pikarsky (The Hebrew University of Jerusalem, Israel) for the gift of the p53-floxed mice and Professor Peter Moeller (University of Ulm, Germany) for the gift of the LiSa-2 cells. C.L. gratefully thanks Professor Noga Kronfeld-Schor (Tel Aviv University, Israel) for useful discussions. C.L. acknowledges grant support from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programmer (grant agreement no. 726225), the I-CORE Gene Regulation in Complex Human Disease Center (no. 41/11) and Israel Science Foundation (ISF) (grant 129/13). C.L. thanks Yuval and Omer Levy for exponential joy and Medina and Elisha Levy for tremendous support. S.P. is the recipient of a 2017 I-core travel scholarship, 4 Djerassi graduate student symposium 2019 award, 2020 student excellence award at the Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, CBRC 2 Zvi and Esther Weinstat Graduate Students 2020 award and EMBO Scientific Exchange Grant (no. 9256). S.P. thanks Smita Sunil Parikh and Rushita Parikh for the journey. Parts of the research in A.W.’s lab is supported by the ISF (grant 1781/16), Israel Ministry of Science and Technology (grants 3-13608 and 84/19) and EPM Inc. th nd

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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