Rev-erbβ Regulates the Expression of Genes Involved in Lipid Absorption in Skeletal Muscle Cells

The skeletal muscle of obese individuals exhibits an impaired ability to increase the expression of genes linked with fatty acid oxidation (FAO) upon lipid exposure. The present study determined if this response could be attributed to differential DNA methylation signatures. RNA and DNA were isolated from primary human skeletal muscle cells (HSkMC) from lean and severely obese women following lipid incubation. mRNA expression and DNA methylation were quantified for genes that globally regulate FAO [PPARγ coactivator ( PGC-1α), peroxisome proliferator-activated receptors ( PPARs), nuclear respiratory factors ( NRFs)]. With lipid oversupply, increases in NRF-1, NRF-2, PPARα, and PPARδ expression were dampened in skeletal muscle from severely obese compared with lean women. The expression of genes downstream of the PPARs and NRFs also exhibited a pattern of not increasing as robustly upon lipid exposure with obesity. Increases in CpG methylation near the transcription start site with lipid oversupply were positively related to PPARδ expression; increases in methylation with lipid were depressed in HSkMC from severely obese women. With severe obesity, there is an impaired ability to upregulate global transcriptional regulators of FAO in response to lipid exposure. Transient changes in DNA methylation patterns and differences in the methylation signature with severe obesity may play a role in the transcriptional regulation of PPARδ in response to lipid. The persistence of differential responses to lipid in HSkMC derived from lean and obese subjects supports the possibility of stable epigenetic programming of skeletal muscle cells by the respective environments.

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The JAK2/STAT3 Signal Pathway Regulates the Expression of Genes Related to Skeletal Muscle Development and Energy Metabolism in Mice and Mouse Skeletal Muscle Cells

Bioscience Biotechnology and Biochemistry ◽

10.1271/bbb.120324 ◽

2012 ◽

Vol 76 (10) ◽

pp. 1866-1870 ◽

Cited By ~ 3

Author(s):

Jing LIU ◽

Xubin JING ◽

Lu GAN ◽

Chao SUN

Keyword(s):

Skeletal Muscle ◽

Energy Metabolism ◽

Muscle Development ◽

Muscle Cells ◽

Signal Pathway ◽

Skeletal Muscle Cells ◽

Skeletal Muscle Development ◽

Mouse Skeletal Muscle ◽

Expression Of Genes

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RORα Regulates the Expression of Genes Involved in Lipid Homeostasis in Skeletal Muscle Cells

Journal of Biological Chemistry ◽

10.1074/jbc.m404927200 ◽

2004 ◽

Vol 279 (35) ◽

pp. 36828-36840 ◽

Cited By ~ 126

Author(s):

Patrick Lau ◽

Susan J. Nixon ◽

Robert G. Parton ◽

George E. O. Muscat

Keyword(s):

Skeletal Muscle ◽

Muscle Cells ◽

Skeletal Muscle Cells ◽

Lipid Homeostasis ◽

Expression Of Genes

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

Biochemistry Research International ◽

10.1155/2012/714074 ◽

2012 ◽

Vol 2012 ◽

pp. 1-12 ◽

Cited By ~ 25

Author(s):

Nataša Nikolić ◽

Magdalena Rhedin ◽

Arild C. Rustan ◽

Len Storlien ◽

G. Hege Thoresen ◽

...

Keyword(s):

Skeletal Muscle ◽

Lipid Metabolism ◽

Mrna Expression ◽

Human Skeletal Muscle ◽

Muscle Cells ◽

Oxidative Capacity ◽

Skeletal Muscle Cells ◽

Expression Of Genes ◽

Human Myotubes ◽

Human Skeletal Muscle Cells

We investigated the effects of PGC-1α(peroxisome proliferator-activated receptorγcoactivator-1α) overexpression on the oxidative capacity of human skeletal muscle cellsex vivo. PGC-1αoverexpression 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 musclein vivo, PGC-1αoverexpression increased expression of several genes, which were downregulated during the process of cell isolation and culturing. In conclusion, PGC-1αoverexpression 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-1αexpression may have utility in treatment of obesity and obesity-related diseases.

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