Unlabelled: 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-C 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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031862 | PMC |
| http://dx.doi.org/10.1016/j.metabol.2019.06.009 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Non-canonical hepatic androgen receptor mediates glucagon sensitivity in female mice through the PGC1α/ERRα/mitochondria axis.
Cell Rep
January 2025
Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China; Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China; Research Center for Industries of the Future, Westlake University, Hangzhou, Zhejiang, China. Electronic address:
Glucagon has recently been found to modulate liver fat content, in addition to its role in regulating gluconeogenesis. However, the precise mechanisms by which glucagon signaling synchronizes glucose and lipid metabolism in the liver remain poorly understood. By employing chemical and genetic approaches, we demonstrate that inhibiting the androgen receptor (AR) impairs the ability of glucagon to stimulate gluconeogenesis and lipid catabolism in primary hepatocytes and female mice.
View Article and Find Full Text PDFThe adiponectin-PPARγ axis in hepatic stellate cells regulates liver fibrosis.
Cell Rep
January 2025
Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address:
Hepatic stellate cells (HSCs) are key drivers of local fibrosis. Adiponectin, conventionally thought of as an adipokine, is also expressed in quiescent HSCs. However, the impact of its local expression on the progression of liver fibrosis remains unclear.
View Article and Find Full Text PDFFoxk2 Enhances Adipogenic Differentiation by Relying on the Transcriptional Activation of Peroxisome Proliferator-Activated Receptor Gamma.
J Cell Mol Med
January 2025
NHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of Endocrinology, Tianjin, China.
Proper differentiation of bone marrow stromal cells (BMSCs) into adipocytes is crucial for maintaining skeletal homeostasis. However, the underlying regulatory mechanisms remain incompletely understood, posing a challenge for the treatment of age-related osteopenia and osteoporosis. Here, through comprehensive gene expression analysis during BMSC differentiation into adipocytes, we identified the forkhead transcription factor Foxk2 as a key regulator of this process.
View Article and Find Full Text PDFYeast Dnm1 causes altered organelle dynamics and sheds light on the human DRP1 disease mechanism.
Mitochondrion
January 2025
Organelle Biology and Cellular Ageing Lab, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India. Electronic address:
Mitochondrial morphology is a result of regulated opposite events called fission and fusion and requires the GTPase, dynamin-related protein 1 (DRP1/Dnm1), or its homologs. A recent clinical report identified a heterozygous missense mutation in the human DRP1 that replaces Glycine (G) 149 with Arginine (R) and results in debilitating conditions in the patient. In this study, we mimicked this mutation in yeast Dnm1 (G178R) and investigated the impact of the pathogenic mutation on the protein's function.
View Article and Find Full Text PDFAnalysis of thyroid function and structure and serum metabolomics in pregnant rats exposed to airborne contaminants: Combined perchlorate, thiocyanate, and nitrate exposure.
Ecotoxicol Environ Saf
January 2025
School of Public Health, Xinjiang Medical University, Urumqi, China. Electronic address:
Objectives: Perchlorates, nitrates, and thiocyanates constitute environmental endocrine disruptors; however, health damage caused by absorption through the respiratory tract remains poorly studied. We investigated the effects of inhalation of these pollutants on thyroid function and structure and serum metabolomics in pregnant rats.
Methods: We established a Sprague-Dawley pregnant rat model exposed to perchlorate, nitrate, and thiocyanate at different gestational stages and compared maternal serum thyroid function levels, foetal development, thyroid morphology, and pathological changes between exposed and non-exposed groups at different concentrations.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!