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

Abstract

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 µmol/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 µmol/l; pioglitazone, 281±40 µmol/l, p=0.03; rosiglitazone, 276±27 µmol/l, p=0.005; RWJ241947, 398±51 µmol/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 µmol/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.

Muscle unloading-induced metabolic remodeling is associated with acute alterations in PPARδ and UCP-3 expression

“…Gastrocnemius muscle was not investigated because Ucp-3 was not found to be differentially expressed in this tissue. Because UCP-3 is thought to be regulated by PPAR␦ (56) and is found primarily in muscle (11,23), we assessed expression of both proteins in soleus muscle after 24-h unloading. A representative Western blot of UCP-3 and PPAR␦ expression in soleus muscle of three ambulatory and five HLS animals is shown in Fig.…”

PPARs in the Control of Uncoupling Proteins Gene Expression

“…Contradictory results have been reported on the action of thiazolidinediones on UCP3 gene expression in myogenic cells, from inhibition [82] to stimulation [83]. Treatment with thiazolidinediones “in vivo” also led to variable effects depending on the type of thiazolidinedione or the length of treatment [33, 57, 84, 85]. Mice with a muscle-specific PPAR γ deletion show unaltered UCP3 gene expression [86].…”

Putative function and physiological relevance of the mitochondrial uncoupling protein-3: Involvement in fatty acid metabolism?

“…In addition, ligands for RXR which heterodimerises with PPAR, also induce UCP3 mRNA expression [44,81,82]. Also in vivo studies showed that UCP3 mRNA can be induced by PPAR agonists in rodents although the results are less straight forward [83][84][85]. So far, no human data have been published on the effect of PPAR agonists on UCP3, however, we recently found that 8 weeks of rosiglitazone treatment increased UCP3 protein content by $25% in skeletal muscle of human diabetic patients (P. Schrauwen, M. Mensink, G. Schaart, E. Moonen-Kornips, J-P. Sels, E.E.…”