Leptin-mediated changes in hepatic mitochondrial metabolism, structure, and protein levels.

TitleLeptin-mediated changes in hepatic mitochondrial metabolism, structure, and protein levels.
Publication TypeJournal Article
Year of Publication2009
AuthorsSingh, A, Wirtz, M, Parker, N, Hogan, M, Strahler, J, Michailidis, G, Schmidt, S, Vidal-Puig, A, Diano, S, Andrews, P, Brand, MD, Friedman, J
JournalProc Natl Acad Sci U S A
Date Published2009 Aug 04
KeywordsAnimals, Body Weight, Fatty Acids, Fatty Liver, Leptin, Male, Mice, Mice, Inbred C57BL, Mice, Obese, Mitochondria, Liver, Mitochondrial Proteins, Oxidation-Reduction, Oxygen Consumption, Phosphorylation, Proteomics

Leptin reduces body weight in ob/ob mice by decreasing food intake and increasing energy expenditure; however, the mechanisms by which it does the latter are not known. Here we report that 30% of the weight loss induced by leptin treatment of ob/ob mice is due to changes in energy expenditure. In assessing leptin's effects on specific tissues, we found that hepatic basal metabolic rate was paradoxically decreased 1.7-fold with leptin treatment, which was the result of a 1.6-fold reduction in mitochondrial volume density and altered substrate oxidation kinetics. The altered kinetics were associated with a decrease in protein levels of 2 mitochondrial respiratory chain components--cytochrome c oxidase subunit VIa and cytochrome c oxidase subunit IV. In addition to reduced hepatic metabolism, there was reduced long chain fatty acid production and a 2.5-fold increase in hepatic lipid export, both of which explain the reduced steatosis in leptin-treated animals. These data help clarify the role of the liver in leptin-mediated weight loss and define the mechanisms by which leptin alters hepatic metabolism and corrects steatosis.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
Citation Key10.1073/pnas.0903723106
PubMed ID19622746
PubMed Central IDPMC2713753
Grant ListG0600717 / / Medical Research Council / United Kingdom
G0802051 / / Medical Research Council / United Kingdom
/ / Howard Hughes Medical Institute / United States