Cellular Retinol-Binding Protein Type I (CRBP-I) Regulates Adipogenesis

Abstract

Adipogenesis is governed by a well-documented cascade of transcription factors. However, less is known about non-transcription factors that govern early stages of adipogenesis. Here we show that cellular retinol-binding protein type I (CRBP-I), a small cytosolic binding protein for retinol and retinaldehyde, is specifically restricted to preadipocytes in white adipose tissue. The absence of CRBP-I in mice (CRBP-I-KO mice) leads to increased adiposity. Despite increased adiposity, CRBP-I-KO mice remain more glucose tolerant and insulin sensitive during high-fat-diet feeding. 3T3-L1 cells deficient in CRBP-I or mouse embryonic fibroblasts derived from CRBP-I-KO mice had increased adipocyte differentiation and triglyceride (TG) accumulation. This was due to increased expression and activity of PPARγ, while other transcription factor pathways in early and late differentiation remained unchanged. Conversely, the overexpression of CRBP-I in 3T3-L1 cells results in decreased TG accumulation. In conclusion, CRBP-I is a cytosolic protein specifically expressed in preadipocytes that regulates adipocyte differentiation in part by affecting PPARγ activity.

We thank H. N. Ginsberg at Columbia University for helpful discussions and critical review of the manuscript, J. L. Napoli at the University of California—Berkeley for performing the retinoid analyses in our cell models, and G. Reyes at Columbia University for technical assistance.

The work was supported by grants RO1 DK-067512 (S. Vogel) and DK-063608-06 (S. Vogel) from the NIDDK and the German Academic Exchange Service (S.K.F.).