Search: WFRF:(Lelliott Christopher J)
> Litwin Sheldon E. >
Ablation of PGC-1be...
Ablation of PGC-1beta results in defective mitochondrial activity, thermogenesis, hepatic function, and cardiac performance
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- Lelliott, Christopher J. (author)
- Department of Clinical Biochemistry, University of Cambridge, Cambridge, United Kingdom; AstraZeneca R&D, Mölndal, Sweden
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- Medina-Gomez, Gema (author)
- Department of Clinical Biochemistry, University of Cambridge, Cambridge, United Kingdom
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- Petrovic, Natasa (author)
- The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden
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- Kis, Adrienn (author)
- Department of Clinical Biochemistry, University of Cambridge, Cambridge, United Kingdom
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- Feldmann, Helena M. (author)
- The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden
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- Bjursell, Mikael (author)
- AstraZeneca R&D, Mölndal, Sweden
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- Parker, Nadeene (author)
- Department of Clinical Biochemistry, University of Cambridge, Cambridge, United Kingdom
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- Curtis, Keira (author)
- Department of Clinical Biochemistry, University of Cambridge, Cambridge, United Kingdom
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- Campbell, Mark (author)
- Department of Clinical Biochemistry, University of Cambridge, Cambridge, United Kingdom
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- Hu, Ping (author)
- Division of Cardiology, University of Utah, Salt Lake City, Utah, United States of America
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- Zhang, Dongfang (author)
- Division of Cardiology, University of Utah, Salt Lake City, Utah, United States of America
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- Litwin, Sheldon E. (author)
- Division of Cardiology, University of Utah, Salt Lake City, Utah, United States of America
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- Zaha, Vlad G. (author)
- Division of Endocrinology, Metabolism, and Diabetes and Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, Utah, United States of America
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- Fountain, Kimberly T. (author)
- Division of Endocrinology, Metabolism, and Diabetes and Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, Utah, United States of America
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- Boudina, Sihem (author)
- Division of Endocrinology, Metabolism, and Diabetes and Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, Utah, United States of America
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- Jimenez-Linan, Mercedes (author)
- Department of Clinical Biochemistry, University of Cambridge, Cambridge, United Kingdom
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- Blount, Margaret (author)
- Department of Clinical Biochemistry, University of Cambridge, Cambridge, United Kingdom
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- Lopez, Miguel (author)
- Department of Clinical Biochemistry, University of Cambridge, Cambridge, United Kingdom
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- Meirhaeghe, Aline (author)
- INSERM, Institut Pasteur de Lille, Lille Cedex, France
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- Bohlooly-Y, Mohammad (author)
- AstraZeneca R&D, Mölndal, Sweden
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- Storlien, Leonard (author)
- AstraZeneca R&D, Mölndal, Sweden
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- Strömstedt, Maria (author)
- AstraZeneca R&D, Mölndal, Sweden
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- Snaith, Michael (author)
- AstraZeneca R&D, Mölndal, Sweden
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- Oresic, Matej, 1967- (author)
- VTT Technical Research Centre of Finland, Espoo, Finland
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- Abel, E. Dale (author)
- Division of Endocrinology, Metabolism, and Diabetes and Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, Utah, United States of America
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- Cannon, Barbara (author)
- The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden
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- Vidal-Puig, Antonio (author)
- Department of Clinical Biochemistry, University of Cambridge, Cambridge, United Kingdom
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(creator_code:org_t)
- 2006-11-07
- 2006
- English.
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In: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 4:11
- Related links:
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https://doi.org/10.1...
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https://journals.plo...
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https://urn.kb.se/re...
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Abstract
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- The transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1beta (PGC-1beta) has been implicated in important metabolic processes. A mouse lacking PGC-1beta (PGC1betaKO) was generated and phenotyped using physiological, molecular, and bioinformatic approaches. PGC1betaKO 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-1beta ablation was partially compensated by up-regulation of PGC-1alpha in BAT and white adipose tissue (WAT) that lead to increased thermogenesis, reduced body weight, and reduced fat mass. Despite their decreased fat mass, PGC1betaKO mice had hypertrophic adipocytes in WAT. The thermogenic role of PGC-1beta was identified in thermoneutral and cold-adapted conditions by inadequate responses to norepinephrine injection. Furthermore, PGC1betaKO hearts showed a blunted chronotropic response to dobutamine stimulation, and isolated soleus muscle fibres from PGC1betaKO mice have impaired mitochondrial function. Lack of PGC-1beta 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-1beta plays a general role in controlling basal mitochondrial function and also participates in tissue-specific adaptive responses during metabolic stress.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Andra medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Other Basic Medicine (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Lelliott, Christ ...
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Medina-Gomez, Ge ...
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Petrovic, Natasa
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Kis, Adrienn
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Feldmann, Helena ...
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Bjursell, Mikael
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show more...
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Parker, Nadeene
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Curtis, Keira
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Campbell, Mark
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Hu, Ping
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Zhang, Dongfang
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Litwin, Sheldon ...
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Zaha, Vlad G.
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Fountain, Kimber ...
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Boudina, Sihem
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Jimenez-Linan, M ...
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Blount, Margaret
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Lopez, Miguel
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Meirhaeghe, Alin ...
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Bohlooly-Y, Moha ...
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Storlien, Leonar ...
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Strömstedt, Mari ...
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Snaith, Michael
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Oresic, Matej, 1 ...
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Abel, E. Dale
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Cannon, Barbara
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Vidal-Puig, Anto ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Other Basic Medi ...
- Articles in the publication
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PLoS biology
- By the university
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Örebro University