UNCOUPLING PROTEIN-3 EXPRESSION IN RODENT SKELETAL-MUSCLE IS MODULATED BY FOOD-INTAKE BUT NOT BY CHANGES IN ENVIRONMENTAL-TEMPERATURE

A new member of the uncoupling protein (UCP) family called UCP3 has re cently been cloned and shown to be highly expressed in skeletal muscle of rodents and humans, In the present study, UCP3 was overexpressed i n C2C12 myoblasts where it acts as an uncoupling protein, Changes in U CP3 mRNA expression were examined in rodent muscles,under conditions k nown to modulate thermogenesis in brown adipose tissue, In skeletal mu scle, UCP3 expression did not change in response to 48 h of cold expos ure (6 degrees C), whereas it was decreased by 81% or increased 5.6-fo ld by 1 week of 50% food restriction or fasting, respectively. It was also decreased by 36% in soleus muscle of obese (fa/fa) as compared wi th lean Zucker rats, The unexpected rise of UCP3 mRNA level induced by fasting did not change in vitro muscle basal heat production rate but decreased by 31% the capacity to produce heat in response to the unco upler carbonyl-cyanide p-trifluoromethoxyphenylhydrazone. This decreas e may reflect underlying uncoupling by UCP3. Upregulation of UCP3 mRNA after a 24-h fast was still observed in mice exposed at thermoneutral ity, These results show that the increase in UCP3 expression induced b y fasting is associated with the maintenance of thermogenesis measured in muscle in vitro and is not modulated by environmental temperature. The notion that UCP3 expression is modulated by food intake is of imp ortance to better understand the pathophysiology of obesity in humans.