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Vol. 273, Issue 1, 5-8, January 2, 1998
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From the Departments of 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 C2C12
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. Up-regulation 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.
Medical Biochemistry and
¶ Physiology, Faculty of Medicine, University of Geneva, 1 Michel
Servet, 1211 Geneva 4, Switzerland
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