PGC-1alpha deficiency causes multi-system energy metabolic derangements: muscle dysfunction, abnormal weight control and hepatic steatosis. Export

@article{citeulike:2909101, abstract = {The gene encoding the transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) was targeted in mice. PGC-1alpha null (PGC-1alpha(-/-)) 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-1alpha(-/-) mice. With age, the PGC-1alpha(-/-) 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-1alpha(-/-) mice, leading to reduced muscle performance and exercise capacity. PGC-1alpha(-/-) mice exhibit a modest diminution in cardiac function related largely to abnormal control of heart rate. The PGC-1alpha(-/-) mice were unable to maintain core body temperature following exposure to cold, consistent with an altered thermogenic response. Following short-term starvation, PGC-1alpha(-/-) mice develop hepatic steatosis due to a combination of reduced mitochondrial respiratory capacity and an increased expression of lipogenic genes. Surprisingly, PGC-1alpha(-/-) 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-1alpha(-/-) mice. These results demonstrate that PGC-1alpha is necessary for appropriate adaptation to the metabolic and physiologic stressors of postnatal life.}, address = {Center for Cardiovascular Research, Washington University School of Medicine, St Louis, Missouri, USA.}, author = {Leone, T. C. and Lehman, J. J. and Finck, B. N. and Schaeffer, P. J. and Wende, A. R. and Boudina, S. and Courtois, M. and Wozniak, D. F. and Sambandam, N. and Bernal-Mizrachi, C. and Chen, Z. and Holloszy, J. O. and Medeiros, D. M. and Schmidt, R. E. and Saffitz, J. E. and Abel, E. D. and Semenkovich, C. F. and Kelly, D. P.}, citeulike-article-id = {2909101}, citeulike-linkout-0 = {http://dx.doi.org/10.1371/journal.pbio.0030101}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/15760270}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=15760270}, doi = {10.1371/journal.pbio.0030101}, issn = {1545-7885}, journal = {PLoS biology}, month = {April}, number = {4}, posted-at = {2009-07-17 14:31:53}, priority = {3}, title = {PGC-1alpha deficiency causes multi-system energy metabolic derangements: muscle dysfunction, abnormal weight control and hepatic steatosis.}, url = {http://dx.doi.org/10.1371/journal.pbio.0030101}, volume = {3}, year = {2005} }

TY - JOUR ID - citeulike:2909101 L3 - citeulike-article-id:2909101 N2 - The gene encoding the transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) was targeted in mice. PGC-1alpha null (PGC-1alpha(-/-)) 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-1alpha(-/-) mice. With age, the PGC-1alpha(-/-) 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-1alpha(-/-) mice, leading to reduced muscle performance and exercise capacity. PGC-1alpha(-/-) mice exhibit a modest diminution in cardiac function related largely to abnormal control of heart rate. The PGC-1alpha(-/-) mice were unable to maintain core body temperature following exposure to cold, consistent with an altered thermogenic response. Following short-term starvation, PGC-1alpha(-/-) mice develop hepatic steatosis due to a combination of reduced mitochondrial respiratory capacity and an increased expression of lipogenic genes. Surprisingly, PGC-1alpha(-/-) 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-1alpha(-/-) mice. These results demonstrate that PGC-1alpha is necessary for appropriate adaptation to the metabolic and physiologic stressors of postnatal life. IS - 4 JF - PLoS biology SN - 1545-7885 AD - Center for Cardiovascular Research, Washington University School of Medicine, St Louis, Missouri, USA. TI - PGC-1alpha deficiency causes multi-system energy metabolic derangements: muscle dysfunction, abnormal weight control and hepatic steatosis. VL - 3 AU - Leone, TC AU - Lehman, JJ AU - Finck, BN AU - Schaeffer, PJ AU - Wende, AR AU - Boudina, S AU - Courtois, M AU - Wozniak, DF AU - Sambandam, N AU - Bernal-Mizrachi, C AU - Chen, Z AU - Holloszy, JO AU - Medeiros, DM AU - Schmidt, RE AU - Saffitz, JE AU - Abel, ED AU - Semenkovich, CF AU - Kelly, DP PY - 2005/04// UR - http://dx.doi.org/10.1371/journal.pbio.0030101 ER -