The effect of TGF?1 on thermogenic markers is dependent on the degree of adipocyte differentiation.

ABSTRACT: Transforming growth factor ? (TGF?) a multifunctional cytokine is known to regulate cell proliferation, differentiation, migration and survival. Although there is variable expression of modulators of TGF? action during differentiation, a differential effect on fat cell metabolism at the different stages of adipocyte differentiation was unclear. In the present study, 3T3L1 cells were used as an in vitro model to study the effect of TGF? on adipogenic and thermogenic markers at various stages of preadipocyte to mature adipocyte differentiation. As in our earlier studies on the effect of TGF? on CEBP's, we used a standard differentiation mix, and one with the addition of rosiglitazone. RhTGF?1 was added to undifferentiated adipocytes (preadipocytes) and to adipocytes at day 0 (commitment stage) as well as day 10 (terminal differentiation). Cellular responses in terms of Pref1, PPAR?, TLE3, PGC1?, PRDM16, UCP1 and UCP2 mRNA levels and selected protein products, were determined. Increases in PPAR?, PRDM16, UCP1 and UCP2 mRNA and decreases in Pref1 are good indicators of successful differentiation. The early addition of rhTGF?1 during commitment stage decreased PPAR?, PRDM16, TLE3, UCP1 and UCP2 mRNA and decreased PRDM16 protein consistent with our earlier report on the inhibition of CEBP's by TGF? and CCN2. The addition of rhTGF?1 to mature adipocyte at day 10 increased UCP1 mRNA and increased PRDM16 and UCP1 proteins. In the present study, our results suggest that TGF?1 added late enhances the thermogenic potential of mature cells and causes 3T3L1 cells to differentiate to resemble brown or beige rather than white adipose tissue.

SUBMITTER: Maharjan BR 

PROVIDER: S-EPMC7225410 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature