G0S2a1 (G0/G1 switch gene 2a1) is downregulated by TNF-α in grass carp (Ctenopharyngodon idellus) hepatocytes through PPARα inhibition.

G0/G1 switch gene 2 plays an important role in the regulation of lipolysis in mammals, but little is known about its gene (G0S2) structure and function in fish. In the present study, two genes, G0S2a and G0S2b were isolated and characterized from grass carp Ctenopharyngodon idella, which encode peptides of 111 and 84 amino acids, respectively. Moreover, alternative multiple exon usage resulted in a significant variation in the 5'-region of G0S2a transcripts yielding two isoforms (G0S2a1 and G0S2a2). Phylogenetic and synteny analyses indicated that G0S2a and G0S2b could have originated from the teleost-specific genome duplication event. Analysis of the exon-intron structures clarified that G0S2a contained an extra intron compared with G0S2b. G0S2a1, G0S2a2 and G0S2b mRNAs were highly expressed in adipose tissue and liver. G0S2a was localized to the cytoplasm and nucleus, while G0S2b was mainly localized in cytoplasm, suggesting that G0S2a and G0S2b may have different functions in grass carp. PPARα agonist caused an increase in G0S2a1 and G0S2b expression, revealing that they are subject to transcriptional control by PPARα-mediated signals. TNF-α treatment decreased G0S2a1 and G0S2a2 transcripts that paralleled TNF-α downregulation of PPARα; however, only the effects of TNF-α on G0S2a1 were attenuated by treatment with PPARα agonist. Our findings identify G0S2a, not G0S2b, as a target gene for TNF-α and reveal that TNF-α suppresses G0S2a1 gene expression through a PPARα-dependent pathway in grass carp hepatocytes.