Molecular cloning and characterization of the anti-obesity gene adipose in pig.

ABSTRACT

Obesity has become an epidemic health problem characterized by aberrant energy metabolism. As the major player in energy homeostasis, adipose tissue has a decisive role in the development of obesity. Many genes involved in adipogenesis are also correlated with obesity. Adipose (Adp) has been established as an anti-obesity gene to repress adipogenesis and fat accumulation in mice, which inhibits the transcriptional activity of PPARγ by forming a chromatin remodeling complex with histones and HDAC3. Here, we reported the cloning and characterization of the pig Adp gene. Pig Adp cDNA had an ORF of 2034 nucleotides and was highly conserved among various species. Genomic sequence analysis indicated that pig Adp gene contains 16 exons and 15 introns, spanning more than 60kb on chromosome 6q21-24. The expression of pig Adp was high in testis, lung, kidney and adipose tissues, and relatively low in skeletal muscle. Bioinformatic analysis of 5'-flanking region of Adp has identified several potential binding sites for pivotal transcriptional factors related to both adipocyte differentiation and inflammation, highlighting the significance of Adp in energy metabolism. We have confirmed that KLF6, a positive regulator of adipogenesis, can enhance the promoter activity of Adp and up-regulate its mRNA expression. Taken together, our results would be helpful for further study of Adp regulation in the process of fat accumulation.