랫드 대상 2,2’-디티오디에탄설폰산의 간대사 관련 유전자 발현

초록

This study aimed to elucidate the hepatic metabolic regulatory mechanisms and in vivo safety of 2,2’-dithiodiethanesulfonic acid, a dimer of coenzyme M. Male and female rats were administered 2,2’-dithiodiethanesulfonic acid via repeat oral gavage at a dose of 1g/kg/day for 28 days, followed by biological pathway analysis and metabolic profiling based on 461 differentially expressed genes (DEGs) in liver tissues compared to the control group. Our results revealed that the compound commonly activated hepatic electron-transfer redox reactions across both sexes, yet induced distinct sexually dimorphic metabolic profiles. Female rats exhibited a predominance of nutrient chemotaxis and cholesterol metabolism, while males showed activation of thioester metabolism and sulfur compound interconversion. Notably, the compound modulates metabolic pathways associated with the methylation of glutamate residues in methyl-accepting chemotaxis proteins. This also regulates the metabolism of the prolyl-tRNA synthetase, which is critical for synthesizing the coenzyme M and cofactor F420 necessary for methanogenesis. Furthermore, the compound participates in the detoxification process mediated by acute phase proteins and innate immune response necessary for restoring homeostasis. Based on these results, the subsequent study will focus on validating the methane reducing efficacy of 2,2’-dithiodiethanesulfonic acid during in vitro enteric fermentation using Hanwoo rumen fluid.

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