Gasotransmitter signaling in energy homeostasis and metabolic disorders

Gasotransmitters are small molecules of gases, including nitric oxide (NO), hydrogen sulfide (H₂S), and carbon monoxide (CO). These three gasotransmitters can be endogenously produced and regulate a wide range of pathophysiological processes by interacting with specific targets upon diffusion in the biological media. By redox and epigenetic regulation of various physiological functions, NO, H₂S, and CO are critical for the maintenance of intracellular energy homeostasis. Accumulated evidence has shown that these three gasotransmitters control ATP generation, mitochondrial biogenesis, glucose metabolism, insulin sensitivity, lipid metabolism, and thermogenesis, etc. Abnormal generation and metabolism of NO, H₂S, and/or CO are involved in various abnormal metabolic diseases, including obesity, diabetes, and dyslipidemia. In this review, we summarized the roles of NO, H₂S, and CO in the regulation of energy homeostasis as well as their involvements in the metabolism of dysfunction-related diseases. Understanding the interaction among these gasotransmitters and their specific molecular targets are very important for therapeutic applications.