Laboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, Greece; Center of Clinical, Experimental Surgery & Translational Research, Biomedical Research Foundation of the Academy of Athens, Greece.
Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA.
Pharmacol Res. 2018 Feb;128:190-199. doi: 10.1016/j.phrs.2017.09.023. Epub 2017 Oct 2.
Hydrogen sulfide (HS) is an endogenously produced signaling molecule synthesized by cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST). Given that HS exerts significant effects on bioenergetics and metabolism, the goal of the current study was to determine the expression of HS-producing enzymes in adipose tissues in models of obesity and metabolic disruption. Mice fed a western diet expressed lower mRNA levels of all three enzymes in epididymal fat (EWAT), while only CSE and 3-MST were reduced in brown adipose tissue (BAT). At the protein level 3-MST was reduced in all fat depots studied. Using db/db mice, a genetic model of obesity, we found that CSE, CBS and 3-MST mRNA were reduced in white fat, while only CSE was reduced in BAT. CBS and CSE protein levels were suppressed in all three fat depots. In a model of age-related weight gain, no reduction in the mRNA of any of the enzymes was noted. Smaller amounts of 3-MST protein were found in EWAT, while both CSE and 3-MST were reduced in BAT. Tissue levels of HS were lower in WAT in HFD mice; both WAT and BAT contained lower HS amounts in db/db animals. Taken together, our data suggest that obesity is associated with a decreased expression of HS-synthesizing enzymes and reduced HS levels in adipose tissues of mice. We propose that the reduction in HS may contribute to the metabolic response associated with obesity. Further work is needed to determine whether restoring HS levels may have a beneficial effect on obesity-associated metabolic alterations.
硫化氢（HS）是一种内源性信号分子，由胱硫醚γ-裂解酶（CSE）、胱硫醚β-合酶（CBS）和 3-巯基丙酮酸硫转移酶（3-MST）合成。鉴于 HS 对生物能量学和代谢有重要影响，本研究旨在确定肥胖和代谢紊乱模型中脂肪组织中 HS 产生酶的表达。喂食西式饮食的小鼠在附睾脂肪（EWAT）中三种酶的 mRNA 水平均降低，而棕色脂肪组织（BAT）中仅 CSE 和 3-MST 降低。在蛋白质水平上，所有研究的脂肪组织中 3-MST 均减少。使用 db/db 小鼠，一种肥胖的遗传模型，我们发现 CSE、CBS 和 3-MST mRNA 在白色脂肪中减少，而在 BAT 中仅 CSE 减少。CBS 和 CSE 蛋白水平在所有三个脂肪组织中均受到抑制。在与年龄相关的体重增加模型中，未发现任何酶的 mRNA 减少。在 EWAT 中发现 3-MST 蛋白减少，而在 BAT 中 CSE 和 3-MST 均减少。在 HFD 小鼠的 WAT 中 HS 组织水平较低；db/db 动物的 WAT 和 BAT 中 HS 含量均较低。总之，我们的数据表明肥胖与 HS 合成酶表达降低和脂肪组织中 HS 水平降低有关。我们提出，HS 的减少可能导致与肥胖相关的代谢反应。需要进一步的工作来确定恢复 HS 水平是否对肥胖相关的代谢改变有益。
