FIG. 7.

(A) Troglitazone selectively activates expression of group 2 genes in 3T3-L1 adipocytes. 3T3-L1 preadipocytes were differentiated using standard conditions, and at day 2, day 4, and day 6, the differentiating cells were exposed to 5 μM troglitazone for 2 days. Untreated and treated cells were harvested for analysis of select mRNAs using RT-PCR as described in Materials and Methods. GAPDH, glyceraldehyde-3-phosphate dehydrogenase. (B) Knockdown of SIRT1 in 3T3-L1 preadipocytes enhances the expression of FGF21 in response to exposure to troglitazone. Control and SIRT1 knockdown 3T3-L1 preadipocytes were differentiated for 4 days, at which time the cells were exposed to the indicated doses of troglitazone for 2 days. Total RNA of the cells was isolated at day 6 and subjected to RT-PCR for analysis of the indicated group 1 and group 2 genes as described in Materials and Methods. (C) Model proposing interplay between PPARγ and SIRT1 in controlling adipocyte function. PPARγ functions to regulate adipocyte formation and function. Endogenous ligands activate PPARγ, requiring participation of both helices 7 and 12 to orchestrate adipogenesis. In mature adipocytes, SIRT1 mediates hormonal and nutrient control of select PPARγ target genes that are involved in controlling metabolism by suppressing the actions of endogenous ligands. The TZD family of synthetic PPARγ ligands can overcome the suppressive effects of SIRT1 acting through helix 7, as well as helix 12, to induce the metabolic genes.