Cysteine and hydrogen sulfide in the regulation of metabolism: Insights from genetics and pharmacology

Obesity and diabetes represent a significant and escalating worldwide health burden. These conditions are characterized by abnormal nutrient homeostasis. One such perturbation is altered metabolism of the sulfur-containing amino acid cysteine. Obesity is associated with elevated plasma cysteine, whereas diabetes is associated with reduced cysteine levels. One mechanism by which cysteine may act is through its enzymatic breakdown to produce hydrogen sulfide (H2 S), a gasotransmitter that regulates glucose and lipid homeostasis. Here we review evidence from both pharmacological studies and transgenic models suggesting that cysteine and hydrogen sulfide play a role in the metabolic dysregulation underpinning obesity and diabetes. We then outline the growing evidence that regulation of hydrogen sulfide levels through its catabolism can impact metabolic health. By integrating hydrogen sulfide production and breakdown pathways we re-assess current hypothetical models of cysteine and hydrogen sulfide metabolism, offering new insight into their roles in the pathogenesis of obesity and diabetes.