1 The Institute of Health Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
2 Department of Endocrinology and Metabolism, Shanghai Institute of Endocrine and Metabolic Diseases, China National Research Center for Metabolic Diseases, Ruijin Hospital, Shanghai JiaoTong University School of Medicine (SJTUSM), Shanghai, China
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Appetite is tightly controlled by neural and hormonal signals in animals. In general, steroid receptor coactivator 1 (SRC1) enhances steroid hormone signalling in energy balance and serves as a common coactivator of several steroid receptors, such as oestrogen and glucocorticoid receptors. However, the key roles of SRC1 in energy balance remain largely unknown. We first confirmed that SRC1 is abundantly expressed in the hypothalamic arcuate nucleus (ARC), which is a critical centre for regulating feeding and energy balance; it is further co-localised with agouti-related protein and proopiomelanocortin neurons in the arcuate nucleus. Interestingly, local SRC1 expression changes with the transition between sufficiency and deficiency of food supply. To identify its direct role in appetite regulation, we repressed SRC1 expression in the hypothalamic ARC using lentivirus shRNA and found that SRC1 deficiency significantly promoted food intake and body weight gain, particularly in mice fed with a high-fat diet. We also found the activation of the AMP-activated protein kinase (AMPK) signalling pathway due to SRC1 deficiency. Thus, our results suggest that SRC1 in the ARC regulates appetite and body weight and that AMPK signalling is involved in this process. We believe that our study results have important implications for recognising the overlapping and integrating effects of several steroid hormones/receptors on accurate appetite regulation in future studies.
Supplementary Figure S1 Distribution of SRC1 in the hypothalamic arcuate nucleus of mice. (A) A representative immunofluorescent staining of SRC1 (red) in coronal hypothalamic sections from AgRP-GFP mice. AgRP neurons are identified by GFP (green) fluorescence. (B) A representative immunofluorescent staining of SRC1 (red) in POMC-GFP mice. POMC neurons are also identified by GFP (green) fluorescence. All the mice were 8 weeks old and males and received a normal chow diet. Twelve sections from three of both types of mice were assessed. All images were generated by laser scanning confocal microscopy. 3V, Third ventricle. Scale bars (A, B), 100 μm.