Overexpression of PGC-1α Increases Fatty Acid Oxidative Capacity of Human Skeletal Muscle Cells

Overexpression of PGC-1α Increases Fatty Acid Oxidative Capacity of Human Skeletal Muscle Cells

We investigated the effects of PGC-1α (peroxisome proliferator-activated receptor γ coactivator-1α) overexpression on the oxidative capacity of human skeletal muscle cells ex vivo. PGC-1α overexpression increased the oxidation rate of palmitic acid and mRNA expression of genes regulating lipid metab...

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Main Authors: Nataša Nikolić, Magdalena Rhedin, Arild C. Rustan, Len Storlien, G. Hege Thoresen, Maria Strömstedt
Format: Article
Language:English
Published: Hindawi Limited 2012-01-01
Series:Biochemistry Research International
Online Access:http://dx.doi.org/10.1155/2012/714074
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spelling doaj-20b17c9d2c514a199005d5b05dec807b2020-11-24T23:55:36ZengHindawi LimitedBiochemistry Research International2090-22472090-22552012-01-01201210.1155/2012/714074714074Overexpression of PGC-1α Increases Fatty Acid Oxidative Capacity of Human Skeletal Muscle CellsNataša Nikolić0Magdalena Rhedin1Arild C. Rustan2Len Storlien3G. Hege Thoresen4Maria Strömstedt5Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, P.O. Box 1068 Blindern, N-0316 Oslo, NorwayAstraZeneca Reseach and Development, SE-43185 Mölndal, SwedenDepartment of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, P.O. Box 1068 Blindern, N-0316 Oslo, NorwayBoden Institute of Obesity, Nutrition and Exercise, University of Sydney, Sydney, NSW 2006, AustraliaDepartment of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, P.O. Box 1068 Blindern, N-0316 Oslo, NorwayAstraZeneca Reseach and Development, SE-43185 Mölndal, SwedenWe investigated the effects of PGC-1α (peroxisome proliferator-activated receptor γ coactivator-1α) overexpression on the oxidative capacity of human skeletal muscle cells ex vivo. PGC-1α overexpression increased the oxidation rate of palmitic acid and mRNA expression of genes regulating lipid metabolism, mitochondrial biogenesis, and function in human myotubes. Basal and insulin-stimulated deoxyglucose uptake were decreased, possibly due to upregulation of PDK4 mRNA. Expression of fast fiber-type gene marker (MHCIIa) was decreased. Compared to skeletal muscle in vivo, PGC-1α overexpression increased expression of several genes, which were downregulated during the process of cell isolation and culturing. In conclusion, PGC-1α overexpression increased oxidative capacity of cultured myotubes by improving lipid metabolism, increasing expression of genes involved in regulation of mitochondrial function and biogenesis, and decreasing expression of MHCIIa. These results suggest that therapies aimed at increasing PGC-1α expression may have utility in treatment of obesity and obesity-related diseases.http://dx.doi.org/10.1155/2012/714074
collection DOAJ
language English
format Article
sources DOAJ
author Nataša Nikolić
Magdalena Rhedin
Arild C. Rustan
Len Storlien
G. Hege Thoresen
Maria Strömstedt
spellingShingle Nataša Nikolić
Magdalena Rhedin
Arild C. Rustan
Len Storlien
G. Hege Thoresen
Maria Strömstedt
Overexpression of PGC-1α Increases Fatty Acid Oxidative Capacity of Human Skeletal Muscle Cells
Biochemistry Research International
author_facet Nataša Nikolić
Magdalena Rhedin
Arild C. Rustan
Len Storlien
G. Hege Thoresen
Maria Strömstedt
author_sort Nataša Nikolić
title Overexpression of PGC-1α Increases Fatty Acid Oxidative Capacity of Human Skeletal Muscle Cells
title_short Overexpression of PGC-1α Increases Fatty Acid Oxidative Capacity of Human Skeletal Muscle Cells
title_full Overexpression of PGC-1α Increases Fatty Acid Oxidative Capacity of Human Skeletal Muscle Cells
title_fullStr Overexpression of PGC-1α Increases Fatty Acid Oxidative Capacity of Human Skeletal Muscle Cells
title_full_unstemmed Overexpression of PGC-1α Increases Fatty Acid Oxidative Capacity of Human Skeletal Muscle Cells
title_sort overexpression of pgc-1α increases fatty acid oxidative capacity of human skeletal muscle cells
publisher Hindawi Limited
series Biochemistry Research International
issn 2090-2247
2090-2255
publishDate 2012-01-01
description We investigated the effects of PGC-1α (peroxisome proliferator-activated receptor γ coactivator-1α) overexpression on the oxidative capacity of human skeletal muscle cells ex vivo. PGC-1α overexpression increased the oxidation rate of palmitic acid and mRNA expression of genes regulating lipid metabolism, mitochondrial biogenesis, and function in human myotubes. Basal and insulin-stimulated deoxyglucose uptake were decreased, possibly due to upregulation of PDK4 mRNA. Expression of fast fiber-type gene marker (MHCIIa) was decreased. Compared to skeletal muscle in vivo, PGC-1α overexpression increased expression of several genes, which were downregulated during the process of cell isolation and culturing. In conclusion, PGC-1α overexpression increased oxidative capacity of cultured myotubes by improving lipid metabolism, increasing expression of genes involved in regulation of mitochondrial function and biogenesis, and decreasing expression of MHCIIa. These results suggest that therapies aimed at increasing PGC-1α expression may have utility in treatment of obesity and obesity-related diseases.
url http://dx.doi.org/10.1155/2012/714074
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AT lenstorlien overexpressionofpgc1aincreasesfattyacidoxidativecapacityofhumanskeletalmusclecells
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