Skin epidermal keratinocyte p53 induces food uptake upon UV exposure

Shivang Parikh; Roma Parikh; Marco Harari; Aron Weller; Lior Bikovski; Carmit Levy

doi:10.3389/fnbeh.2023.1281274

Skin epidermal keratinocyte p53 induces food uptake upon UV exposure

Front Behav Neurosci. 2023 Dec 12:17:1281274. doi: 10.3389/fnbeh.2023.1281274. eCollection 2023.

Authors

Shivang Parikh^#¹, Roma Parikh¹, Marco Harari^{2

3}, Aron Weller⁴, Lior Bikovski^{5

6}, Carmit Levy¹

Affiliations

¹ Department of Human Genetics and Biochemistry, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
² Dead Sea and Arava Science Center, Masada DMZ Medical Center, Ein Bokek, Israel.
³ Faculty of Medicine, Hebrew University, Jerusalem, Israel.
⁴ Department of Psychology and the Gonda Brain Research Center, Bar-Ilan University, Ramat Gan, Israel.
⁵ The Myers Neuro-Behavioral Core Facility, Tel Aviv University, Tel Aviv, Israel.
⁶ School of Behavioral Sciences, Netanya Academic College, Netanya, Israel.

^# Contributed equally.

Abstract

Introduction: The first cells affected by UVB exposure are epidermal keratinocytes, and p53, the genome guardian, is activated in these cells when skin is exposed to UVB. UVB exposure induces appetite, but it remains unclear whether p53 in epidermal keratinocytes plays a role in this appetite stimulation.

Results: Here we found that food intake was increased following chronic daily UVB exposure in a manner that depends on p53 expression in epidermal keratinocytes. p53 conditional knockout in epidermal keratinocytes reduced food intake in mice upon UVB exposure.

Methods: To investigate the effects of p53 activation following UVB exposure, mice behavior was assessed using the staircase, open-field, elevated-plus maze, and conditioned-place preference tests. In addition to effects on appetite, loss of p53 resulted in anxiety-related behaviors with no effect on activity level.

Discussion: Since skin p53 induces production of β-endorphin, our data suggest that UVB-mediated activation of p53 results in an increase in β-endorphin levels which in turn influences appetite. Our study positions UVB as a central environmental factor in systemic behavior and has implications for the treatment of eating and anxiety-related disorders.

Keywords: UVB exposure; anxiety-related behaviors; conditioned-place preference; epidermal keratinocytes; food intake motivation; mice; p53 activation.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. CL acknowledges grant support from the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Program (grant agreement no. 726225), the I-CORE Gene Regulation in Complex Human Disease Center (no. 41/11), Israel Science Foundation (ISF) (grant 129/13) and the UTI – Dead Sea Research Institute grant. SP is the recipient of a 2017 I-core Travel Scholarship, 4th Djerassi Graduate Student Symposium 2019 Award, 2020 Student Excellence Award at the Department of Human Genetics and Biochemistry, Faculty of Medicine, Tel Aviv University, CBRC 2nd Zvi and Esther Weinstat Graduate Student 2020 Award, and EMBO Scientific Exchange Grant (no. 9256). Research in AW’s lab was supported in part by the ISF (grant 1781/16) and the Israel Ministry of Science and Technology (grants 3–13608 and 84/19).