Regulation of adipocyte differentiation by nuclear hormone receptors
Molecular events which control adipocyte differentiation or proliferation are poorly understood. Using an in vitro model system, the 3T3-L1 cell line, we have characterized the role of various nuclear hormone receptors in adipocyte differentiation. During adipose conversion multiple nuclear hormone receptors alter their pattern of expression. While the orphan receptor, Rev-Erb, is induced early in adipogenesis, retinoic acid receptor (RAR) isoform $\gamma$1 is specifically down regulated early in this process. Ectopic expression of RAR$\gamma$1 can prevent preadipocytes from differentiating into adipocytes. This inhibition is isoform- and subtype-specific because neither RAR$\gamma$2 nor RAR$\alpha$1 can functionally susbstitute for RAR$\gamma$1. Interestingly, functional antagonism of RARs by a dominant negative RAR is sufficient to initiate the adipogenic program, indicating that RAR$\gamma$1 may have a critical role in keeping the preadipocyte from differentiating prematurely. Furthermore, peroxisome proliferators, which activate peroxisome proliferator activated receptors (PPARs), can independently initiate adipogenesis. mPPAR$\gamma$ is induced during adipogenesis and is expressed with adipose tissue specificity. Retinoid X receptor $\alpha$ (RXR$\alpha$), a heterodimerization partner for mPPAR$\gamma$, is also upregulated early in adipocyte differentiation. Conditional expression of RXR$\alpha$ results in adipose conversion in the absence of other adipogenic hormones, suggesting that PPAR$\gamma$/RXR$\alpha$ heterodimer may be critical in initiating adipose conversion. Collectively, our data show that multiple nuclear hormone receptors play a pivotal role in regulating adipocyte differentiation.
Anatomy & physiology|Animals
Chawla, Ajay, "Regulation of adipocyte differentiation by nuclear hormone receptors" (1996). Dissertations available from ProQuest. AAI9627898.