Expression of uncoupling protein-3 mRNA in rat skeletal muscle is acutely stimulated by thiazolidinediones:: an exercise-like effect?

Aims/hypothesis. We examined whether thiazolidinediones (TZDs) acutely affect uncoupling protein-3 (UCP-3) expression in skeletal muscle and plasma NEFA in Sprague-Dawley rats. Methods. Expression of UCP-3 mRNA in hindlimb muscles and plasma NEFA were measured after a single intraperitoneal injection of TZDs in healthy male rats. Results. Independent of which TZD was injected (50 mumol/kg), UCP-3 expression in gastrocnemius muscle was distinctly increased after 6 h (increase vs vehicle-injected control: pioglitazone, 10.3+/-3.2-fold, p=0.03; rosiglitazone, 8.7+/-1.2-fold, p=0.001; RWJ241947, 9.5+/-2.7-fold, p=0.03). This was accompanied by elevated plasma NEFA (control 158+/-13 mumol/l; pioglitazone, 281+/-40 mumol/l, p=0.03; rosiglitazone, 276+/-27 mumol/l, p=0.005; RWJ241947, 398+/-51 mumol/l, p=0.004). The increase in plasma NEFA could in part have mediated TZD-induced UCP-3 expression, but increased UCP-3 mRNA was also found in isolated muscle after 2 h of TZD exposure in vitro (25 mumol/l pioglitazone, 1.7+/-0.3-fold, p=0.046), suggesting that TZDs act directly and independently of NEFA on skeletal muscle. Conclusions/interpretation. In healthy rats, a single dose of TZDs rapidly increases UCP-3 mRNA in skeletal muscle and plasma NEFA. This effect resembles the acute response to a bout of exercise.