Uncoupling Protein-3 Expression in Rodent Skeletal Muscle Is Modulated by Food Intake but Not by Changes in Environmental Temperature

Abstract

A new member of the uncoupling protein (UCP) family called UCP3 has recently been cloned and shown to be highly expressed in skeletal muscle of rodents and humans. In the present study, UCP3 was overexpressed in C 2 C 12 myoblasts where it acts as an uncoupling protein.Changes in UCP3 mRNA expression were examined in rodent muscles under conditions known to modulate thermogenesis in brown adipose tissue. In skeletal muscle, UCP3 expression did not change in response to 48 h of cold exposure (6°C), whereas it was decreased by 81% or increased 5.6-fold 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 with 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 uncoupler carbonylcyanide p-trifluoromethoxyphenylhydrazone. This decrease may reflect underlying uncoupling by UCP3. Upregulation of UCP3 mRNA after a 24-h fast was still observed in mice exposed at thermoneutrality. These results show that the increase in UCP3 expression induced by 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 importance to better understand the pathophysiology of obesity in humans.

The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP

“…The present data indicate that UCP2, UCP3, StUCP and AtUCP alter the mitochondrial membrane potential recorded in i o in recombinant yeast and mammalian cells, and probably uncouple respiration [17,30,31,57,[59][60][61]84,85]. The respiration of isolated yeast mitochondria into which UCP2 had been introduced was less coupled than that of control mitochondria [30].…”

“…There is agreement that cold exposure does not activate UCP3 mRNA expression in skeletal muscle, indicating that this protein is not primarily implicated in body temperature regulation [84,178,207]. The significance of high levels of UCP2 mRNA in white fat and of UCP3 mRNA in skeletal muscle of hibernating squirrels is unknown [209].…”

“…In itro and in i o experiments demonstrated that fatty acids or certain retinoids promote UCP2 and\or UCP3 expression in white and brown adipocytes, myocytes and pancreatic islets [171,172,177,206,[229][230][231][232][233][234][235][236][237][238]. Expression of UCP2 and\or UCP3 in skeletal muscles, heart or adipose tissue can be induced by various situations characterized by elevated levels of circulating non-esterified fatty acids, such as starvation in humans or rodents [84,169,239,240], high-fat feeding in rodents [30,177] and genetic or experimental diabetes in rodents [31,241,242]. It is not known whether the very high level of ketone bodies observed in diabetic rats is related to UCP induction [241].…”

Effect of Cheonggukjang supplementation upon hepatic acyl-CoA synthase, carnitine palmitoyltransferase I, acyl-CoA oxidase and uncoupling protein 2 mRNA levels in C57BL/6J mice fed with high fat diet

“…Uncoupling proteins (UCPs) are mitochondrial inner membrane proteins. Uncoupling proteins allow the dissipation of part of the proteon electrochemical gradient generated by the electron transfer chain across the mitochondrial inner membrane and can thus increase heat production by uncoupling respiration from ATP synthesis [1]. Uncoupling protein 2 (UCP2) mRNA is expressed in numerous types of tissue such as liver, skeletal muscle, heart, and kidney.…”

Energetics and longevity in birds

“…Homologues and possible functions of UCPs have been previously described (Boss et al 1998;Ricquier and Bouillaud 2000;Brand and Esteves 2005;Sokolova and Sokolov 2005;Echtay 2007). The attenuation of ROS production has received much attention as a likely function of UCPs (Echtay and Brand 2007).…”