Novel hypothalamic pathways for metabolic effects of spexin
Penghua Fang, Yuqing She, Mei Yu, Jing Yan, Xizhong Yu, Juan Zhao, Jin Yu, Min Wen, Wenbin Shang, Zhenwen Zhang
Abstract
One of the main underlying etiologies of type 2 diabetes (T2DM) is insulin resistance, which is most frequently caused by obesity. Notably, the deregulation of adipokine secretion from visceral adiposity has been identified as a crucial characteristic of type 2 diabetes and obesity. Spexin is an adipokine that is released by many different tissues, including white adipocytes and the glandular stomach, and is negatively connected with the state of energy storage. This peptide acts through GALR2/3 receptors to control a wide range of metabolic processes, including inflammation, browning, lipolysis, energy expenditure, and eating behavior. Specifically, spexin can enter the hypothalamus and regulate the hypothalamic melanocortin system, which in turn balances energy expenditure and food intake. This review examines recent advances and the underlying mechanisms of spexin in obesity and T2DM. In particular, we address a range of topics from basic research to clinical findings, such as an analysis of the possible function of spexin in the hypothalamic melanocortin response, which involves reducing energy intake and increasing energy expenditure while also enhancing insulin sensitivity and glucose tolerance. Gaining more insight into the mechanisms that underlie the spexin system's control over energy metabolism and homeostasis may facilitate the development of innovative treatment approaches that focus on combating obesity and diabetes. • Spexin ameliorates systemic insulin resistance in obesity and type 2 diabetes. • The hypothalamic melanocortin system is a critical component of the spexin/GALR2/3 downstream signaling network. • Spexin reduces energy intake and increases energy expenditure by the GALR2/3-melanocortin signaling axis.