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. Research Methods and Procedures: Sprague–Dawley rats w...

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Published in:Obesity (Silver Spring, Md.) Md.), 2001-05, Vol.9 (5), p.313-319
Main Authors: Chou, Chieh J., Cha, Ming C., Jung, Dennis W., Boozer, Carol N., Hashim, Sami A., Pi‐Sunyer, F. Xavier
Format: Article
Language:English
Subjects:
Animals
Calorimetry, Indirect
Carrier Proteins - metabolism
Dietary Fats - administration & dosage
Dietary Fats - pharmacology
energy expenditure
Energy Metabolism
Fatty Acids, Nonesterified - blood
high‐fat diet
Ion Channels
Leptin - blood
Male
Mitochondria, Muscle - metabolism
Mitochondrial Proteins
mitochondrial swelling
Muscle, Skeletal - metabolism
Permeability
Random Allocation
Rats
Uncoupling Protein 3
Up-Regulation
Western blot
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Summary: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. Research Methods and Procedures: 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. Discussion: 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.
ISSN:1930-7381
1071-7323
1930-739X
1550-8528
DOI:10.1038/oby.2001.39