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© 2005 Leone et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Citation: Leone TC, Lehman JJ, Finck BN, Schaeffer PJ, Wende AR, et al. (2005) PGC-1? Deficiency Causes Multi-System Energy Metabolic Derangements: Muscle Dysfunction, Abnormal Weight Control and Hepatic Steatosis. PLoS Biol 3(4): e101. doi:10.1371/journal.pbio.0030101

Abstract

The gene encoding the transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) was targeted in mice. PGC-1α null (PGC-1α-/-) mice were viable. However, extensive phenotyping revealed multi-system abnormalities indicative of an abnormal energy metabolic phenotype. The postnatal growth of heart and slow-twitch skeletal muscle, organs with high mitochondrial energy demands, is blunted in PGC-1α-/- mice. With age, the PGC-1α-/- mice develop abnormally increased body fat, a phenotype that is more severe in females. Mitochondrial number and respiratory capacity is diminished in slow-twitch skeletal muscle of PGC-1α-/- mice, leading to reduced muscle performance and exercise capacity. PGC-1α-/- mice exhibit a modest diminution in cardiac function related largely to abnormal control of heart rate. The PGC-1α-/- mice were unable to maintain core body temperature following exposure to cold, consistent with an altered thermogenic response. Following short-term starvation, PGC-1α-/- mice develop hepatic steatosis due to a combination of reduced mitochondrial respiratory capacity and an increased expression of lipogenic genes. Surprisingly, PGC-1α-/- mice were less susceptible to diet-induced insulin resistance than wild-type controls. Lastly, vacuolar lesions were detected in the central nervous system of PGC-1α-/- mice. These results demonstrate that PGC-1α is necessary for appropriate adaptation to the metabolic and physiologic stressors of postnatal life.

Details

Title
PGC-1[alpha] Deficiency Causes Multi-System Energy Metabolic Derangements: Muscle Dysfunction, Abnormal Weight Control and Hepatic Steatosis
Author
Leone, Teresa C; Lehman, John J; Finck, Brian N; Schaeffer, Paul J; Wende, Adam R; Boudina, Sihem; Courtois, Michael; Wozniak, David F; Sambandam, Nandakumar; Bernal-Mizrachi, Carlos; Chen, Zhouji; Holloszy, John O; Medeiros, Denis M; Schmidt, Robert E; Saffitz, Jeffrey E; Abel, E Dale; Semenkovich, Clay F; Kelly, Daniel P
Pages
e101
Section
Research Article
Publication year
2005
Publication date
Apr 2005
Publisher
Public Library of Science
ISSN
15449173
e-ISSN
15457885
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1292209365
Copyright
© 2005 Leone et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Citation: Leone TC, Lehman JJ, Finck BN, Schaeffer PJ, Wende AR, et al. (2005) PGC-1? Deficiency Causes Multi-System Energy Metabolic Derangements: Muscle Dysfunction, Abnormal Weight Control and Hepatic Steatosis. PLoS Biol 3(4): e101. doi:10.1371/journal.pbio.0030101