Journal article
Ablation of PGC-1β Results in Defective Mitochondrial Activity, Thermogenesis, Hepatic Function, and Cardiac Performance
PLoS biology, Vol.4(11), pp.2042-2056
11/2006
DOI: 10.1371/journal.pbio.0040369
PMID: 17090215
Abstract
The transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1β (PGC-1β) has been implicated in important metabolic processes. A mouse lacking PGC-1β (PGC1βKO) was generated and phenotyped using physiological, molecular, and bioinformatic approaches. PGC1βKO mice are generally viable and metabolically healthy. Using systems biology, we identified a general defect in the expression of genes involved in mitochondrial function and, specifically, the electron transport chain. This defect correlated with reduced mitochondrial volume fraction in soleus muscle and heart, but not brown adipose tissue (BAT). Under ambient temperature conditions, PGC-1β ablation was partially compensated by up-regulation of PGC-1α in BAT and white adipose tissue (WAT) that lead to increased thermogenesis, reduced body weight, and reduced fat mass. Despite their decreased fat mass, PGC1βKO mice had hypertrophic adipocytes in WAT. The thermogenic role of PGC-1β was identified in thermoneutral and cold-adapted conditions by inadequate responses to norepinephrine injection. Furthermore, PGC1βKO hearts showed a blunted chronotropic response to dobutamine stimulation, and isolated soleus muscle fibres from PGC1βKO mice have impaired mitochondrial function. Lack of PGC-1β also impaired hepatic lipid metabolism in response to acute high fat dietary loads, resulting in hepatic steatosis and reduced lipoprotein-associated triglyceride and cholesterol content. Altogether, our data suggest that PGC-1β plays a general role in controlling basal mitochondrial function and also participates in tissue-specific adaptive responses during metabolic stress.
The authors conduct an in-depth analysis of a PGC-1β knockout mouse; these animals posses specific defects in basal mitochondrial function and adaptation to metabolic stress.
Details
- Title: Subtitle
- Ablation of PGC-1β Results in Defective Mitochondrial Activity, Thermogenesis, Hepatic Function, and Cardiac Performance
- Creators
- Christopher J Lelliott - Department of Clinical Biochemistry, University of Cambridge, Cambridge, United KingdomGema Medina-Gomez - Department of Clinical Biochemistry, University of Cambridge, Cambridge, United KingdomNatasa Petrovic - The Wenner-Gren Institute, Stockholm University, Stockholm, SwedenAdrienn Kis - Department of Clinical Biochemistry, University of Cambridge, Cambridge, United KingdomHelena M Feldmann - The Wenner-Gren Institute, Stockholm University, Stockholm, SwedenMikael Bjursell - AstraZeneca R&D, Mölndal, SwedenNadeene Parker - Department of Clinical Biochemistry, University of Cambridge, Cambridge, United KingdomKeira Curtis - Department of Clinical Biochemistry, University of Cambridge, Cambridge, United KingdomMark Campbell - Department of Clinical Biochemistry, University of Cambridge, Cambridge, United KingdomPing Hu - Division of Cardiology, University of Utah, Salt Lake City, Utah, United States of AmericaDongfang Zhang - Division of Cardiology, University of Utah, Salt Lake City, Utah, United States of AmericaSheldon E Litwin - Division of Cardiology, University of Utah, Salt Lake City, Utah, United States of AmericaVlad G Zaha - Division of Endocrinology, Metabolism, and Diabetes and Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, Utah, United States of AmericaKimberly T Fountain - Division of Endocrinology, Metabolism, and Diabetes and Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, Utah, United States of AmericaSihem Boudina - Division of Endocrinology, Metabolism, and Diabetes and Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, Utah, United States of AmericaMercedes Jimenez-Linan - Department of Clinical Biochemistry, University of Cambridge, Cambridge, United KingdomMargaret Blount - Department of Clinical Biochemistry, University of Cambridge, Cambridge, United KingdomMiguel Lopez - Department of Clinical Biochemistry, University of Cambridge, Cambridge, United KingdomAline Meirhaeghe - INSERM, Institut Pasteur de Lille, Lille Cedex, FranceMohammad Bohlooly-Y - AstraZeneca R&D, Mölndal, SwedenLeonard Storlien - AstraZeneca R&D, Mölndal, SwedenMaria Strömstedt - AstraZeneca R&D, Mölndal, SwedenMichael Snaith - AstraZeneca R&D, Mölndal, SwedenMatej Orešič - VTT Technical Research Centre of Finland, Espoo, FinlandE. Dale Abel - Division of Endocrinology, Metabolism, and Diabetes and Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, Utah, United States of AmericaBarbara Cannon - The Wenner-Gren Institute, Stockholm University, Stockholm, SwedenAntonio Vidal-Puig - Department of Clinical Biochemistry, University of Cambridge, Cambridge, United Kingdom
- Resource Type
- Journal article
- Publication Details
- PLoS biology, Vol.4(11), pp.2042-2056
- DOI
- 10.1371/journal.pbio.0040369
- PMID
- 17090215
- NLM abbreviation
- PLoS Biol
- ISSN
- 1544-9173
- eISSN
- 1545-7885
- Publisher
- Public Library of Science; San Francisco, USA
- Alternative title
- Phenotype of the PGC-1β Knockout Mouse
- Language
- English
- Date published
- 11/2006
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984024533902771
Metrics
22 Record Views