DIET-INDUCED CHANGES IN UNCOUPLING PROTEINS IN OBESITY-PRONE AND OBESITY-RESISTANT STRAINS OF MICE

Uncoupling protein 2 (UCP2) maps to a region on distal mouse chromosom e 7 that has been linked to the phenotypes of obesity and type II diab etes, We recently reported that UCP2 expression is increased by high f at feeding in adipose tissue of the A/J strain of mice, which is resis tant to the development of dietary obesity: More recently, a third UCP (UCP3) was identified, which Is expressed largely in skeletal muscle and brown adipose tissue, The UCP2 and UCP3 genes are located adjacent to one another on mouse chromosome 7, Thus, the roles of these UCPs i n both metabolic efficiency and the linkage to obesity and diabetes sy ndromes is unclear, For this reason, we examined the expression of UCP 2 and UCP3 in white adipose tissue and interscapular brown adipose tis sue and in gastrocnemius/soleus muscle preparations from the obesity-r esistant A/J and C57BL/KsJ (KsJ) strains and the obesity-prone C57BL/6 J (B6) mouse strain, In both KsJ and A/J mice, UCP2 expression in whit e fat was increased approximate to 2-fold in response to 2 weeks of a high fat diet, but there was no effect of diet on UCP2 levels in B6 mi ce, In skeletal muscle and in brown fat, neither UCP2 nor UCP3 express ion was affected by diet in A/J, B6, or KsJ mice, However, in brown fa t, we observed a 2-3-fold increase in the expression of UCP1 in respon se to dietary fat challenge, which may be related to diet-induced elev ations in plasma leptin levels, Together, these results indicate that the consumption of a high fat diet selectively regulates UCP2 expressi on In white fat and UCP1 expression In brown fat and that resistance t o obesity is correlated with this early, selective induction of UCP1 a nd UCP2 and is not associated with changes in expression of UCP3.