Expression of uncoupling protein-3 mRNA in rat skeletal muscle is acutely stimulated by thiazolidinediones: an exercise-like effect?
OBJECTIVE
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 micromol/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 micromol/l; pioglitazone, 281+/-40 micromol/l, p=0.03; rosiglitazone, 276+/-27 micromol/l, p=0.005; RWJ241947, 398+/-51 micromol/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 micromol/l pioglitazone, 1.7+/-0.3-fold, p=0.046), suggesting that TZDs act directly and independently of NEFA on skeletal muscle.


CONCLUSIONS
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.
Brunmair
B
B
Department of Medicine III, Division of Endocrinology & Metabolism, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
Gras
F
F
Wagner
L
L
Artwohl
M
M
Zierhut
B
B
Waldhäusl
W
W
Fürnsinn
C
C
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D007473:Ion Channels; D008297:Male; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D000077205:Pioglitazone; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D014158:Transcription, Genetic; D000071247:Uncoupling Protein 3
D002352:Carrier Proteins; D007473:Ion Channels; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D045162:Thiazolidinediones; C000604394:Ucp3 protein, rat; D000071247:Uncoupling Protein 3; D000077154:Rosiglitazone; D000077205:Pioglitazone