硫化氢（H₂S）在脂肪细胞和脂肪组织中内源性产生并刺激脂肪形成。然而，H₂S 对肥胖症发展的综合致病作用及其潜在机制尚不清楚。本研究发现降低的内源性H₂S水平降低了小鼠脂肪细胞中的脂质积累。在脂肪形成诱导6 d 后，外源性H₂S 处理显著增加了原代小鼠前脂肪细胞的脂肪生成。在脂肪生成的早
期阶段，H₂S增加细胞增殖并为细胞增生做好准备。H₂S处理10 d 后，前脂肪细胞的细胞表面积和直径明显增大，表明细胞肥大。虽然H₂S 刺激脂质积累和脂肪生成，但H₂S 对脂肪分解没有影响。随着营养过载和高葡萄糖/胰岛素孵化，H₂S 进一步刺激葡萄糖消耗并恶化脂肪细胞肥大。H₂S 上调增生基因[CCAAT/增强子结合蛋白（C/EBPβ）、细胞分裂周期25（Cdc25）、微染色体维持3（Mcm3）和细胞分裂周期（Cdc45）]和细胞周期蛋白依赖性激酶2 蛋白（Cdk2），调节细胞增殖。H₂S 还上调了胰岛素受体β（Irβ）激活的丝裂原活化蛋白激酶（MAPK）和蛋白激酶B（Akt）通路，从而导致脂肪生成。总之，H₂S 增加脂肪细胞分化、肥大和增生，提示它在肥胖症中起致病作用。

Hydrogen sulfide (H₂S) is endogenously produced in adipocytes and fat tissues and stimulates adipogenesis. The integrated pathogenic effects of H₂S on the development of obesity and the underlying mechanisms, however, have been unclear. Here, we find that a decreased endogenous H₂S level lowered lipid accumulation in mouse adipocytes. Exogenous H₂S treatment significantly increased the adipogenesis of primary mouse preadipocytes after six days of adipogenic induction. In the early phase of adipogenesis, H₂S increased cell proliferation and prepared cells to go through hyperplasia. After H₂S treatment for ten days, preadipocytes exhibited significantly greater cell surface area and diameter, indicating cell hypertrophy. Although it stimulated lipid accumulation and adipogenesis, H₂S had no effect on lipolysis. With nutrition overload and high glucose/insulin incubation, H₂S further stimulated glucose consumption and deteriorated adipocyte hypertrophy. H₂S upregulated hyperplasia genes (CCAAT/enhancer-binding protein (C/EBPβ), cell division cycle 25 (Cdc25), minichromosome maintenance 3 (Mcm3), and cell division cycle (Cdc45)) and cyclin-dependent kinase 2 protein (Cdk2), which regulates cell proliferation. H₂S also upregulated the insulin receptor β (Irβ)-activated mitogen-activated protein kinase (MAPK) and protein kinase B (Akt) pathways, leading to adipogenesis. In conclusion, H₂S increases adipocyte differentiation, hypertrophy, and hyperplasia, implying that it plays a pathogenic role in obesity disorder.