Accumulation of lipid droplets (LDs) induces cardiac dysfunctions in type 2 diabetes patients. Recent studies have shown that hydrogen sulphide (H₂S) ameliorates cardiac functions in db/db mice, but its regulation on the formation of LDs in cardiac tissues is unclear. Db/db mice were injected with NaHS (40 μmol·kg^-1) for twelve weeks. H9c2 cells were treated with high glucose (40 mmol/L), oleate (200 µmol/L), palmitate (200 µmol/L) and NaHS (100 µmol/L) for 48 hours. Plasmids for the overexpression of wild-type Hrd1 and Hrd1 mutated at Cys115 were constructed. The interaction between Hrd1 and DGAT1 and DGAT2, the ubiquitylation level of DGAT1 and 2, the S-sulfhydration of Hrd1 were measured. Exogenous H₂S ameliorated the cardiac functions, decreased ER stress and reduced the number of LDs in db/db mice. Exogenous H₂S could elevate the ubiquitination level of DGAT 1 and 2 and increased the expression of Hrd1 in cardiac tissues of db/db mice. The S-sulfhydration of Hrd1 by NaHS enhanced the interaction between Hrd1 and DGAT1 and 2 to inhibit the formation of LD. Our findings suggested that H₂S modified Hrd1 S-sulfhydration at Cys115 to reduce the accumulation of LDs in cardiac tissues of db/db mice.

中文翻译：

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硫化氢通过 Hrd1 S-硫化减少 db/db 小鼠心脏组织中脂滴的积累

脂滴 (LD) 的积累会导致 2 型糖尿病患者出现心脏功能障碍。最近的研究表明，硫化氢 (H ₂ S) 可改善 db/db 小鼠的心脏功能，但其对心脏组织中 LDs 形成的调节作用尚不清楚。Db/db小鼠注射NaHS (40 μmol·kg ^-1 ) 12周。H9c2 细胞用高葡萄糖 (40 mmol/L)、油酸 (200 µmol/L)、棕榈酸 (200 µmol/L) 和 NaHS (100 µmol/L) 处理 48 小时。构建了用于在 Cys115 突变的野生型 Hrd1 和 Hrd1 过表达的质粒。测量了Hrd1和DGAT1和DGAT2之间的相互作用，DGAT1和2的泛素化水平，Hrd1的S-硫化。外源 H ₂S 改善了 db/db 小鼠的心脏功能，减少了 ER 压力并减少了 LD 的数量。外源性H ₂ S可以提高db/db小鼠心脏组织中DGAT 1和2的泛素化水平，增加Hrd1的表达。NaHS对Hrd1的S-硫化增强了Hrd1与DGAT1和2之间的相互作用，从而抑制了LD的形成。我们的研究结果表明，H ₂ S 修饰了 Cys115 处的 Hrd1 S-硫化作用，以减少 db/db 小鼠心脏组织中 LD 的积累。