UCP3 regulates cardiac efficiency and mitochondrial coupling in high fat-fed mice but not in leptin-deficient mice.
These studies investigate the role of uncoupling protein 3 (UCP3) in cardiac energy metabolism, cardiac O(2) consumption (MVO(2)), cardiac efficiency (CE), and mitochondrial uncoupling in high fat (HF)-fed or leptin-deficient mice. UCP3KO and wild-type (WT) mice were fed normal chow or HF diets for 10 weeks. Substrate utilization rates, MVO(2), CE, and mitochondrial uncoupling were measured in perfused working hearts and saponin-permeabilized cardiac fibers, respectively. Similar analyses were performed in hearts of ob/ob mice lacking UCP3 (U3OB mice). HF increased cardiac UCP3 protein. However, fatty acid (FA) oxidation rates were similarly increased by HF diet in WT and UCP3KO mice. By contrast, MVO(2) increased in WT, but not in UCP3KO with HF, leading to increased CE in UCP3KO mice. Consistent with increased CE, mitochondrial coupling was increased in the hearts of HF-fed UCP3KO mice. Unexpectedly, UCP3 deletion in ob/ob mice reduced FA oxidation but had no effect on MVO(2) or CE. In addition, FA-induced mitochondrial uncoupling was similarly enhanced in U3OB compared with ob/ob hearts and was associated with elevated mitochondrial thioesterase-1 protein content. These studies show that although UCP3 may mediate mitochondrial uncoupling and reduced CE after HF feeding, it does not mediate uncoupling in leptin-deficient states.
Division of Endocrinology, Metabolism, and Diabetes and Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA. sihem.boudina@hmbg.utah.edu
Sihem
S
Boudina
Yong Hwan
YH
Han
Shaobo
S
Pei
Timothy J
TJ
Tidwell
Brandon
B
Henrie
Joseph
J
Tuinei
Curtis
C
Olsen
Sandra
S
Sena
E Dale
ED
Abel
D000818:Animals; D004041:Dietary Fats / Q000009:adverse effects; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology*; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D020738:Leptin / Q000172:deficiency* / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D010101:Oxygen Consumption / Q000235:genetics / Q000502:physiology*; D010170:Palmitoyl-CoA Hydrolase / Q000378:metabolism; D000071247:Uncoupling Protein 3
D004041:Dietary Fats; D007473:Ion Channels; D020738:Leptin; D024101:Mitochondrial Proteins; C000604393:Ucp3 protein, mouse; D000071247:Uncoupling Protein 3; D010170:Palmitoyl-CoA Hydrolase