两性异形是造成健康和行为方面深刻的代谢差异的原因。雄性和雌性对环境线索(如太阳紫外线(UV)暴露)的反应是否不同尚不清楚。

UVB照射导致皮肤脂肪细胞中p53的ghrelin转录激活，而小鼠中有条件敲除p53则会消除UVB诱导的ghrelin表达和食物寻求行为。在雌性中，雌激素会干扰ghrelin启动子上的p53染色质相互作用，从而阻断UVB暴露下的ghrelin和食物寻求行为。这些结果确定皮肤作为能量平衡的主要中介，并可能导致治疗内分泌相关疾病的基于性别的治疗机会。

证据表明，阳光照射会诱发食物寻求行为，食物摄入，以及男性的食物寻求行为和食物摄入，但女性不会。在小鼠中，中波紫外线暴露导致觅食行为增加，食物摄入和体重增加，并对雄性表现出性别二态性。在小鼠和人类男性中，食欲的增加都与循环中的胃饥饿素水平升高有关。

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.

原文链接

https://www.nature.com/articles/s42255-022-00587-9

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