A mitochondria-targeted vitamin E derivative decreases hepatic oxidative stress and inhibits fat deposition in mice.
Our objective in this study was to determine whether a mitochondria-targeted vitamin E derivative (MitoVit E) would decrease oxidative stress and associated obesity by preventing a previously proposed aconitase inhibition cascade. Sixty-four mice were fed a high-fat (HF) diet for 5 wk. They were then switched to either a low-fat (LF) or a medium-fat (MF) diet and gavaged with MitoVit E (40 mg MitoVit E x kg body weight(-1)) or drug vehicle (10% ethanol in 0.9% NaCl solution) every other day for 5 wk. Epididymal fat weight, as well as liver lipid and remaining carcass lipid, were significantly lower in the MF group receiving MitoVit E (MF-E) than in the MF group receiving vehicle only (MF-C). Liver mitochondrial H(2)O(2) production and the protein carbonyl level were also significantly lower in MF-E than in MF-C mice. In contrast, none of the biochemical variables (aconitase activity, ATP and H(2)O(2) production, and protein carbonyl level) in the muscle mitochondria were modified by MitoVit E in either MF or LF groups. Expression of acetyl-CoA carboxylase and fatty acid synthase in both liver and adipose tissue of MF groups was not affected by MitoVit E. However, expression of carnitine palmitoyltransferase 1a in the liver and uncoupling protein 2 in adipose tissue were significantly enhanced by MitoVit E in both LF and MF groups. In conclusion, MitoVit E attenuates hepatic oxidative stress and inhibits fat deposition in mice but not through alleviation of the aconitase inhibition cascade.
Mao
Gaowei
G
Interdepartmental Graduate Program in Nutritional Sciences, Iowa State University, Ames, IA 50011, USA.
Kraus
George A
GA
Kim
Ikyon
I
Spurlock
Michael E
ME
Bailey
Theodore B
TB
Zhang
Qijing
Q
Beitz
Donald C
DC
D000154:Aconitate Hydratase / Q000037:antagonists & inhibitors / Q000235:genetics; D000255:Adenosine Triphosphate / Q000378:metabolism; D000273:Adipose Tissue / Q000033:anatomy & histology / Q000378:metabolism*; D000818:Animals; D001823:Body Composition; D001835:Body Weight; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage; D004435:Eating; D064429:Fatty Acid Synthases / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000378:metabolism; D008055:Lipids / Q000032:analysis; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008930:Mitochondria, Liver / Q000201:enzymology / Q000378:metabolism; D008931:Mitochondria, Muscle / Q000201:enzymology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000648:ultrastructure; D009765:Obesity / Q000517:prevention & control; D009929:Organ Size / Q000187:drug effects; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000032:analysis; D014451:Ubiquinone / Q000008:administration & dosage / Q000494:pharmacology
D004041:Dietary Fats; D008055:Lipids; C478642:MitoVit E; D009943:Organophosphorus Compounds; D012333:RNA, Messenger; D014451:Ubiquinone; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D064429:Fatty Acid Synthases; D000154:Aconitate Hydratase