Fig. 8.

Overexpression of TRB3 decreases peroxisome proliferator-activated receptor-α (PPAR-α), fatty acid transport protein (FATP), and uncoupling protein 3 (UCP3). To determine whether TRB3 regulates PPAR-α, TRB3 and PPAR-α were overexpressed in HEK293 cells. In some experiments, transfected cells were incubated with proteasome inhibitor MG132 overnight before harvesting. A: expression of TRB3 and PPAR-α were determined by Western blotting. Protein was isolated from gastrocnemius muscles from WT and TRB3 TG mice and Western blots were performed to determine protein expression of PPA-α (B), UCP3 (C), and FATP1 (D). E: proposed mechanisms by which TRB3 regulates muscle fiber type and exercise capacity. Overexpression of TRB3 decreased PPAR-α activity and increased the expression of miR208b and miR499, inducing a transformation toward a more oxidative fiber type, which in turn, contributes to increased exercise capacity in TRB3 TG mice (E). Data are means ± SE, n = 8 mice/group for A and n = 3 separate experiments for A. *P < 0.05, PPAR-α compared with PPAR-α +TRB3, #P < 0.05 PPAR-α +TRB3 untreated compared with PPAR-α +TRB3 treated with MG132.