Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, China.
Department of Clinical Laboratory, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Front Endocrinol (Lausanne). 2022 Dec 9;13:1051797. doi: 10.3389/fendo.2022.1051797. eCollection 2022.
The intestinal microbiota and its derived short-chain fatty acids (SCFAs) can reverse obesity and obesity-related metabolic diseases, but whether it has an effect on obesity complicated by precocious puberty and its potential mechanism need to be further understood. The purpose of this study was to investigate the effect of the gut microbiota and its derived short-chain fatty acids (SCFAs) on obesity-induced precocious puberty rats and their regulatory mechanisms. We constructed obesity-induced precocious puberty rats using a high-fat diet (HFD) had notable similarity to precocious puberty caused by obesity due to overeating in children. We then added acetate, propionate, butyrate or their mixture to the HFD, and investigated the effect of intestinal microbiota and its derived SCFAs on the hypothalamic-pituitary-gonadal axis (HPGA) in rats with obesity-induced precocious puberty. We found that obesity-induced precocious puberty rats had an early first estrous cycle, increased hypothalamic mRNA expression of Kiss1, GPR54 and GnRH, and early gonadal maturation. Meanwhile, the intestinal microbiota imbalance and the main SCFAs production decreased in the colon. The addition of acetate, propionate, butyrate or their mixture to the HFD could significantly reverse the precocious puberty of rats, reduce GnRH release from the hypothalamus and delay the development of the gonadal axis through the Kiss1-GPR54-PKC-ERK1/2 pathway. Our findings suggest that gut microbiota-derived SCFAs are promising therapeutic means for the prevention of obesity-induced precocious puberty and provide new therapeutic strategies with clinical value.
肠道微生物群及其衍生的短链脂肪酸（SCFAs）可以逆转肥胖和肥胖相关代谢疾病，但它是否对肥胖合并性早熟及其潜在机制有影响还需要进一步研究。本研究旨在探讨肠道微生物群及其衍生的短链脂肪酸（SCFAs）对肥胖诱导性性早熟大鼠的影响及其调节机制。我们构建了肥胖诱导性性早熟大鼠模型，该模型使用高脂肪饮食（HFD），与儿童因过度饮食引起的肥胖性早熟具有显著相似性。然后，我们在 HFD 中添加乙酸盐、丙酸盐、丁酸盐或它们的混合物，研究了肠道微生物群及其衍生的 SCFAs 对肥胖诱导性性早熟大鼠下丘脑-垂体-性腺轴（HPGA）的影响。我们发现，肥胖诱导性性早熟大鼠出现了早期初情期，下丘脑 Kiss1、GPR54 和 GnRH 的 mRNA 表达增加，性腺过早成熟。同时，结肠中的肠道微生物群失衡和主要 SCFAs 产生减少。在 HFD 中添加乙酸盐、丙酸盐、丁酸盐或它们的混合物可以显著逆转大鼠的性早熟，通过 Kiss1-GPR54-PKC-ERK1/2 通路减少下丘脑 GnRH 的释放并延迟性腺轴的发育。我们的研究结果表明，肠道微生物群衍生的 SCFAs 是预防肥胖诱导性性早熟的有前途的治疗手段，并为具有临床价值的治疗提供了新的策略。
