High-fat diet feeding elevates skeletal muscle uncoupling protein 3 levels but not its activity in rats.
OBJECTIVE
The objective of this study is to test the impact of high-fat diet (HFD) feeding on skeletal muscle (SM) uncoupling protein 3 (UCP3) expression and its association with mitochondrial ion permeability and whole-body energy homeostasis.


METHODS
Sprague-Dawley rats were fed ad libitum either a HFD (60% of energy from fat, n = 6) or a low-fat diet (12% of energy from fat, n = 6) for 4 weeks. Twenty-four-hour energy expenditure was measured by indirect calorimetry in the last week of the dietary treatment. Blood samples were collected for plasma leptin and free fatty acid assays, and mitochondria were isolated from hindlimb SM for subsequent determinations of UCP3 levels and mitochondrial ion permeability.


RESULTS
Plasma leptin levels were higher in rats fed the HFD despite the same body weight in two groups. The same dietary treatment also rendered a 2-fold increase in plasma free fatty acid and SM UCP3 protein levels (Western blot) compared with the group fed the low-fat diet. However, the elevated UCP3 protein levels did not correlate with mitochondrial swelling rates, a measure of mitochondrial chloride, and proton permeability, or with 24-hour energy expenditure.


CONCLUSIONS
The high correlation between the levels of plasma free fatty acid levels and SM UCP3 suggests that circulating free fatty acid may play an important role in UCP3 expression during the HFD feeding. However, the dissociation between the UCP3 protein levels and 24-hour energy expenditure as well as mitochondrial ion permeability suggests that mitochondrial proton leak mediated by muscle UCP3 may not be a major contributor in energy balance in HFD feeding, and other regulatory mechanisms independent of gene regulation may be responsible for the control of UCP3-mediated uncoupling activity.
Chou
C J
CJ
Obesity Research Center, St. Luke's/Roosevelt Hospital Center and Columbia University College of Physicians and Surgeons, New York, New York, USA. jasonc@intra.niddk.nih.gov
Cha
M C
MC
Jung
D W
DW
Boozer
C N
CN
Hashim
S A
SA
Pi-Sunyer
F X
FX
D000818:Animals; D002153:Calorimetry, Indirect; D002352:Carrier Proteins / Q000378:metabolism*; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology*; D004734:Energy Metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D007473:Ion Channels; D020738:Leptin / Q000097:blood; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism*; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000378:metabolism*; D010539:Permeability; D011897:Random Allocation; D051381:Rats; D000071247:Uncoupling Protein 3; D015854:Up-Regulation
D002352:Carrier Proteins; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D007473:Ion Channels; D020738:Leptin; D024101:Mitochondrial Proteins; C000604394:Ucp3 protein, rat; D000071247:Uncoupling Protein 3