Upregulation of hypothalamic TRPV4 via S100a4/AMPKα signaling pathway promotes the development of diet-induced obesity

Obesity is associated with abnormal regulation of energy metabolism in the hypothalamus. Transient receptor potential vanilloid 4 (TRPV4) is involved in regulating osmotic pressure, temperature and mechanical force transmission, but little is known about its role in obesity. Herein, the present study aimed to elucidate the effect of hypothalamic TRPV4 on high-fat diet-induced obesity (DIO) and evaluate its potential for regulating energy metabolism. Here we show that hypothalamic TRPV4 content is increased in DIO rats. Central administration of adeno-associated virus expressing TRPV4 in these animals remarkably increased body weight and fat mass by activating the S100a4/AMPK alpha signaling pathway, thereby promoting positive energy metabolism. Overex-pressed hypothalamic TRPV4 impaired glucose tolerance, while promoting the accumulation of fat in liver cells, resulting in hepatic steatosis. In addition, the upregulation of hypothalamic TRPV4 reduces high-fat induced central inflammation. This study provides evidence that hypothalamic TRPV4 plays a significant role in regu-lating homeostasis. Hypothalamic TRPV4 emerges as a target for therapeutic intervention against obesity.

Automated summary

The study reveals the significant role of hypothalamic TRPV4 in obesity. Overexpressed hypothalamic TRPV4 leads to weight gain, fat accumulation, and hepatic steatosis, while reducing central inflammation induced by high-fat diet. This suggests that hypothalamic TRPV4 could serve as a potential target for therapeutic intervention against obesity.