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Updated: Jan 23, 2026
Human Skeletal Muscle Biopsy Procedures Using the Modified Bergström Technique
Published on: September 10, 2014
Peroxisomal gene and protein expression increase in response to a high-lipid challenge in human skeletal muscle
Tai-Yu Huang1, Donghai Zheng2, Robert C Hickner3
1Department of Kinesiology, East Carolina University, Greenville, NC, United States of America.
Insights
Human skeletal muscle (HSkM) adapts to excess lipids by increasing peroxisomal function. This study shows peroxisomal gene expression and protein levels rise with lipid content, suggesting a key role in muscle lipid metabolism.
Area of Science:
- Cell Biology
- Metabolic Research
- Human Physiology
Background:
- Peroxisomes are vital for lipid metabolism, and their dysfunction can be fatal.
- Little is known about peroxisome adaptation to lipid changes in human skeletal muscle (HSkM).
Purpose of the Study:
- To investigate if HSkM increases peroxisomal gene/protein expression and function in response to lipid oversupply.
- To determine the adaptive role of peroxisomes in HSkM lipid metabolism.
Main Methods:
- Analyzed HSkM biopsies from 62 subjects.
- Correlated peroxisomal proteins and function with intramyocellular lipid content (IMLC).
- Assessed peroxisomal gene expression after high-fat meals and in cultured myotubes treated with fatty acids.
Main Results:
- Fasting HSkM showed correlations between IMLC and peroxisomal biogenesis factor PEX19, and between lipid content and fatty acid oxidation.
- High-fat meals upregulated several PEX genes.
- Fatty acid treatment increased PMP70 protein and mRNA levels of key metabolic genes in HSkM cells.
Conclusions:
- This study provides the first evidence linking IMLC with peroxisomal gene expression and function in HSkM.
- Results suggest peroxisomes play an adaptive role in managing lipid metabolism within human skeletal muscle.
Abstract:
Peroxisomes are essential for lipid metabolism and disruption of liver peroxisomal function results in neonatal death. Little is known about how peroxisomal content and activity respond to changes in the lipid environment in human skeletal muscle (HSkM).
Aims:
We hypothesized and tested that increased peroxisomal gene/protein expression and functionality occur in HSkM as an adaptive response to lipid oversupply.
Materials And Methods:
HSkM biopsies, derived from a total of sixty-two subjects, were collected for 1) examining correlations between peroxisomal proteins and intramyocellular lipid content (IMLC) as well as between peroxisomal functionality and IMLC, 2) assessing peroxisomal gene expression in response to acute- or 7-day high fat meal (HFM), and in human tissue derived primary myotubes for 3) treating with high fatty acids to induce peroxisomal adaptions. IMLC were measured by both biochemical analyses and fluorescent staining. Peroxisomal membrane protein PMP70 and biogenesis gene (PEX) expression were assessed using western blotting and realtime qRT-PCR respectively. 1-14C radiolabeled lignocerate and palmitate oxidation assays were performed for peroxisomal and mitochondrial functionality respectively.
Results:
1) Under fasting conditions, HSkM tissue demonstrated a significant correlation (P ≪ 0.05) between IMCL and the peroxisomal biogenesis factor 19 (PEX19) protein as well as between lipid content and palmitate and lignocerate complete oxidation. 2) Similarly, post-HFM, additional PEX genes (Pex19, PEX11A, and PEX5) were significantly (P ≪ 0.05) upregulated. 3) Increments in PMP70, carnitine octanoyl transferase (CrOT), PGC-1α, and ERRα mRNA were observed post-fatty acid incubation in HSkM cells. PMP70 protein was significantly (P ≪ 0.05) elevated 48-h post lipid treatment.
Conclusions:
These results are the first to associate IMLC with peroxisomal gene/protein expression and function in HSkM suggesting an adaptive role for peroxisomes in lipid metabolism in this tissue.
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