The Peroxisome Proliferator-activated Receptor γ Regulates Expression of the Perilipin Gene in Adipocytes

Recent studies have shown that lipid droplets are covered with a proteinaceous coat, although the functions and identities of the component proteins have not yet been well elucidated. The first identified lipid droplet-specific proteins are the perilipins, a family of proteins coating the surfaces of lipid droplets of adipocytes. The generation of perilipin-null mice has revealed that although they consume more food than control mice, they have normal body weight and are resistant to diet-induced obesity. In one study (Martinez-Botas, J., Anderson, J. B., Tessier, D., Lapillonne, A., Chang, B. H. J., Quast, M. J., Gorenstein, D., Chen, K. H., and Chan, L. (2000) Nat. Genet. 26, 474–479) it was reported that in an animal model obesity was reversible by breeding perilipin –/– alleles into Lepr db/db obese mice, ostensibly by increasing the metabolic rate of the mice. To understand the exact mechanisms that drive the exclusive expression of the perilipin gene in adipocytes, we analyzed the 5′-flanking region of the mouse gene. Treatment of differentiating 3T3-L1 adipocytes with an agonist of proliferator-activated receptor (PPAR) γ, the putative “master regulator” of adipocyte differentiation, significantly augmented perilipin gene expression. Reporter assays using the –2.0-kb promoter revealed that this region contains a functional PPARγ-responsive element. Gel mobility shift and chromatin immunoprecipitation assays showed that endogenous to the perilipin an in adipocytes, was to the the family and the that perilipin gene expression in differentiating adipocytes by into the of and gene well to a of the perilipin gene Recent studies have shown that lipid droplets are covered with a proteinaceous coat, although the functions and identities of the component proteins have not yet been well elucidated. The first identified lipid droplet-specific proteins are the perilipins, a family of proteins coating the surfaces of lipid droplets of adipocytes. The generation of perilipin-null mice has revealed that although they consume more food than control mice, they have normal body weight and are resistant to diet-induced obesity. In one study (Martinez-Botas, J., Anderson, J. B., Tessier, D., Lapillonne, A., Chang, B. H. J., Quast, M. J., Gorenstein, D., Chen, K. H., and Chan, L. (2000) Nat. Genet. 26, 474–479) it was reported that in an animal model obesity was reversible by breeding perilipin –/– alleles into Lepr db/db obese mice, ostensibly by increasing the metabolic rate of the mice. To understand the exact mechanisms that drive the exclusive expression of the perilipin gene in adipocytes, we analyzed the 5′-flanking region of the mouse gene. Treatment of differentiating 3T3-L1 adipocytes with an agonist of proliferator-activated receptor (PPAR) γ, the putative “master regulator” of adipocyte differentiation, significantly augmented perilipin gene expression. Reporter assays using the –2.0-kb promoter revealed that this region contains a functional PPARγ-responsive element. Gel mobility shift and chromatin immunoprecipitation assays showed that endogenous to the perilipin an in adipocytes, was to the the family and the that perilipin gene expression in differentiating adipocytes by into the of and gene well to a of the perilipin gene are the of in the of in the lipid droplets covered by a of and In of by proliferator-activated proliferator-activated element. in of by The are a of proteins the of lipid droplets in adipocytes and J. and have been to of by a to J. L. J. are by and this has been to to lipid droplets L. M. J. J. have revealed that perilipin mice have and of in J. L. Nat. Genet. 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