Brown Adipose Vanin-1 is Required for the Maintenance of Mitochondrial Homeostasis and Prevents Diet-Induced Metabolic Dysfunction

Obesity, a chronic disease, is associated with a disruption of the exquisite balance between energy intake and energy expenditure. Energy dissipating brown adipocytes holds an enormous potential to improve metabolic health. Here, we investigate the role of Vanin-1, a pantetheinase, in regulating mitochondrial respiration. Vanin-1 is found in the mitochondria of brown adipocytes, where adaptive thermogenesis takes place. Vanin-1 knockdown induce whitening in brown adipose tissue (BAT), while over expression of Vanin-1 significantly enhances energy expenditure and thermogenesis in BAT, renders mice resistant to diet-induced obesity. The mechanism behind this is that Vanin-1 deficiency impairs the electron transport chain (ETC) in mitochondria, resulting in reduced mitochondrial respiration. However, treatment with cysteamine restores mitochondrial function and promotes adaptive thermogenesis. Collectively, these findings suggest that Vanin-1 plays a crucial role in promoting mitochondrial respiration to counteract diet-induced obesity, making it a potential therapeutic target for obesity.