Carter Roderick N, Morton Nicholas M
Molecular Metabolism Group, University/BHF Centre for Cardiovascular Sciences, Queens Medical Research Institute, University of Edinburgh, UK.
J Pathol. 2016 Jan;238(2):321-32. doi: 10.1002/path.4659. Epub 2015 Nov 13.
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 sulphur-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 sulphide (H2S), a gasotransmitter that regulates glucose and lipid homeostasis. Here we review evidence from both pharmacological studies and transgenic models suggesting that cysteine and hydrogen sulphide play a role in the metabolic dysregulation underpinning obesity and diabetes. We then outline the growing evidence that regulation of hydrogen sulphide levels through its catabolism can impact metabolic health. By integrating hydrogen sulphide production and breakdown pathways, we re-assess current hypothetical models of cysteine and hydrogen sulphide metabolism, offering new insight into their roles in the pathogenesis of obesity and diabetes.
肥胖和糖尿病是全球范围内日益严重且不断升级的健康负担。这些病症的特征是营养稳态异常。其中一种干扰是含硫氨基酸半胱氨酸的代谢改变。肥胖与血浆半胱氨酸水平升高有关，而糖尿病则与半胱氨酸水平降低有关。半胱氨酸可能发挥作用的一种机制是通过其酶促分解产生硫化氢（H2S），硫化氢是一种调节葡萄糖和脂质稳态的气体信号分子。在此，我们综述了来自药理学研究和转基因模型的证据，表明半胱氨酸和硫化氢在肥胖和糖尿病所基于的代谢失调中发挥作用。然后，我们概述了越来越多的证据，即通过硫化氢的分解代谢来调节其水平会影响代谢健康。通过整合硫化氢的产生和分解途径，我们重新评估了当前关于半胱氨酸和硫化氢代谢的假设模型，为它们在肥胖和糖尿病发病机制中的作用提供了新的见解。
