Deciphering the molecular mediators of triclosan-induced lipid accumulation: Intervention via short-chain fatty acids and miR-101a

As a potential environmental obesogen, triclosan (TCS) carries inherent risks of inducing obesity and metabolic disorders. However, the underlying molecular mechanisms behind the lipid metabolism disorder induced by TCS have remained elusive. Through a fusion of transcriptomics and microRNA target prediction, we hypothesize that miR-101a as a responsive miRNA to TCS exposure in zebrafish, playing a central role in disturbing lipid homeostasis. As an evidence, TCS exposure triggers a reduction in miR-10a expression that accompanied by elevation of genes linked to regulation of lipid homeostasis. Through precision-controlled interventions involving miRNA expression modulation, we discovered that inhibition of miR-101a enhanced expression of its target genes implicated in lipid homeostasis, subsequently triggering excessive fat accumulation. Meanwhile, the overexpression of miR-101a acts as a protective mechanism, counteracting the lipid metabolism disorder induced by TCS in the larvae. Notably, the combination of short-chain fatty acids (SCFAs) emerged as a potential remedy to alleviate TCS-induced lipid accumulation partially by counteracting the decline in miR-101a expression induced by TCS. These revelations provide insight into a prospective molecular framework underlying TCS-triggered lipid metabolism disorders, thereby paving the way for pre-emptive strategies in combating the ramifications of TCS pollution. [Display omitted] •TCS exposure led to hepatic lipid accumulation in zebrafish.•SCFAs emerged as a potential remedy to counter TCS-induced lipid accumulation.•Down regulation of miR-101a caused lipid accumulation as TCS exposure.•MiR-101a acted as a key player in TCS-induced lipid metabolism disorder.•Overexpression of miR-101a was a protector against TCS induced lipid accumulation.