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 (GOS2) structure and function in fish. In the present study, two genes, GOS2a and GOS2b 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 GOS2a transcripts yielding two isoforms (GOS2a1 and GOS2a2). Phylogenetic and synteny analyses indicated that GOS2a and GOS2b could have originated from the teleost-specific genome duplication event. Analysis of the exon intron structures clarified that GOS2a contained an extra intron compared with GOS2b. GOS2a1, GOS2a2 and GOS2b mRNAs were highly expressed in adipose tissue and liver. GOS2a was localized to the cytoplasm and nucleus, while GOS2b was mainly localized in cytoplasm, suggesting that GOS2a and GOS2b may have different functions in grass carp. PPAR alpha agonist caused an increase in GOS2a1 and GOS2b expression, revealing that they are subject to transcriptional control by PPAR alpha-mediated signals. TNF-alpha treatment decreased GOS2a1 and GOS2a2 transcripts that paralleled TNF-alpha downregulation of PPAR alpha; however, only the effects of TNF-alpha on GOS2a1 were attenuated by treatment with PPAR alpha agonist. Our findings identify GOS2a, not GOS2b, as a target gene for TNF-alpha and reveal that TNF-alpha suppresses GOS2a1 gene expression through a PPAR alpha-dependent pathway in grass carp hepatocytes.