TY - JOUR
T1 - Peroxisomal gene and protein expression increase in response to a high-lipid challenge in human skeletal muscle
AU - Huang, Tai Yu
AU - Zheng, Donghai
AU - Hickner, Robert C.
AU - Brault, Jeffrey J.
AU - Cortright, Ronald N.
N1 - Funding Information:
This work was supported in part by a seed grant from the Diabetes Obesity Institute, East Carolina University (RNC), NIH R15HL113854 (RCH) and R01 AR070200 (JJB).
Funding Information:
The authors are grateful to Dr. Sanghee Park, Ph.D. (East Carolina University) for assistance with human skeletal muscle cell culture. This work was supported in part by a seed grant from the Diabetes Obesity Institute, East Carolina University (RNC), NIH R15HL113854 (RCH) and R01 AR070200 (JJB). R.N.C. T.-Y. H. and D. Z. conceived and designed the research study; T.-Y. H. R.C.H. D. Z. and J.J.B. performed the experiments; T.-Y. H. and D. Z. and J.J.B. analyzed the data; T.-Y. H. R.N.C. and D.Z. interpreted the results of experiments; T.-Y. H. and R.N.C. jointly drafted the manuscript; T.-Y.H. R.N.C. D.Z. and R.C.H. edited and revised the manuscript; T.-Y. H. R.N.C. D.Z. R.C.H. and J.J.B. approved the final version of manuscript; T.-Y. H. and J.J.B. prepared the figures.
Publisher Copyright:
© 2019
PY - 2019/9
Y1 - 2019/9
N2 - 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.
AB - 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.
KW - Human primary myotubes
KW - Lignoceric acid oxidation
KW - Lipotoxicity
KW - Mitochondrial β-oxidation
KW - Obesity
UR - http://www.scopus.com/inward/record.url?scp=85067701085&partnerID=8YFLogxK
U2 - 10.1016/j.metabol.2019.06.009
DO - 10.1016/j.metabol.2019.06.009
M3 - Article
C2 - 31226353
AN - SCOPUS:85067701085
SN - 0026-0495
VL - 98
SP - 53
EP - 61
JO - Metabolism: clinical and experimental
JF - Metabolism: clinical and experimental
ER -
