Search Results

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.

Although circulating ghrelin levels correlate inversely with adiposity at baseline, little is known about the effect of percent visceral adipose tissue value (PVATV) on ghrelin expression and secretion in response to fasting. Our study demonstrated that ghrelin increased with 24-h fasting in rats with the lowest PVATV (less than 6%), after 3 days in rats with intermediate PVATV (6–9%) and 5 days in rats with the highest PVATV (greater than 9%). Ghrelin mRNA in the stomach was increased after 3 days in low-PVATV (5.8±0.9%) rats but not in high-PVATV (14±1.6%) rats. Therefore, both ghrelin secretion and mRNA were delayed in response to fasting in rats with increased visceral fat. In rats matched for PVATV, but with different body weights, the fasting induced similar levels of increased ghrelin while in rats with different PVATV ghrelin secretion was different in response to fasting, even when body weights were matched in two groups. These data suggested that the initial PVATV, not lean mass, was related to the pattern of plasma ghrelin in response to fasting in rats.

Vascular endothelial growth factor (VEGF) plays a pivotal role in angiogenesis in ovaries, particularly during follicular development and ovulation. Interleukin-6 (IL-6) is one of the major pro-inflammatory factors that are involved in the angiogenesis process physiologically and pathologically. Previous studies have shown that 17β-estradiol (E2) stimulates VEGF expression by upregulating hypoxia-inducible factor 1α (HIF-1α) in many cell types, and the high level of E2 causes an inflammatory-like microenvironment before ovulation. However, whether IL-6 signaling is involved in E2-regulating VEGF expression in swine granulosa cells (GCs) is still unknown. In this study, we found the estrogen membrane receptor, G-protein-coupled estrogen receptor 1 (GPER), was expressed in swine GCs, and the expression level of GPER, HIF-1α, and VEGF increased with follicular development. In vitro study showed that E2, ICI182780, and GPER agonist (G1) promoted the expressions of HIF-1α and VEGF in swine GCs, while GPER antagonist (G15) inhibited the stimulating effect of E2 and G1. Meanwhile, G15 inhibited the stimulating effect of E2 and G1 on IL-6 mRNA expression and secretion. Furthermore, IL-6 antibody and AG490 (JAK2/STAT3 inhibitor) attenuated G1-induced HIF-1α and VEGF expression. In conclusion, this study revealed how estrogen-induced HIF-1α and VEGF expressions in swine GCs are mediated through GPER-derived IL-6 secretion leading to JAK2/STAT3 activation.