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Omega-3 fatty acid EPA improves regenerative capacity of mouse skeletal muscle cells exposed to saturated fat and inflammation.

ABSTRACT: Sarcopenic obesity is characterised by high fat mass, low muscle mass and an elevated inflammatory environmental milieu. We therefore investigated the effects of elevated inflammatory cytokine TNF-? (aging/obesity) and saturated fatty acid, palmitate (obesity) on skeletal muscle cells in the presence/absence of EPA, a-3 polyunsaturated fatty acid with proposed anti-inflammatory, anti-obesity activities. In the present study we show that palmitate was lipotoxic, inducing high levels of cell death and blocking myotube formation. Cell death under these conditions was associated with increased caspase activity, suppression of differentiation, reductions in both creatine kinase activity and gene expression of myogenic factors; IGF-II, IGFBP-5, MyoD and myogenin. However, inhibition of caspase activity via administration of Z-VDVAD-FMK (caspase-2), Z-DEVD-FMK (caspase-3) and ZIETD-KMK (caspase 8) was without effect on cell death. By contrast, lipotoxicity associated with elevated palmitate was reduced with the MEK inhibitor PD98059, indicating palmitate induced cell death was MAPK mediated. These lipotoxic conditions were further exacerbated in the presence of inflammation via TNF-? co-administration. Addition of EPA under cytotoxic stress (TNF-?) was shown to partially rescue differentiation with enhanced myotube formation being associated with increased MyoD, myogenin, IGF-II and IGFBP-5 expression. EPA had little impact on the cell death phenotype observed in lipotoxic conditions but did show benefit in restoring differentiation under lipotoxic plus cytotoxic conditions. Under these conditions Id3 (inhibitor of differentiation) gene expression was inversely linked with survival rates, potentially indicating a novel role of EPA and Id3 in the regulation of apoptosis in lipotoxic/cytotoxic conditions. Additionally, signalling studies indicated the combination of lipo- and cyto-toxic effects on the muscle cells acted through ceramide, JNK and MAPK pathways and blocking these pathways using PD98059 (MEK inhibitor) and Fumonisin B1 (ceramide inhibitor) significantly reduced levels of cell death. These findings highlight novel pathways associated with in vitro models of lipotoxicity (palmitate-mediated) and cytotoxicity (inflammatory cytokine mediated) in the potential targeting of molecular modulators of sarcopenic obesity.

SUBMITTER: Saini A

PROVIDER: S-EPMC5288450 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Omega-3 fatty acid EPA improves regenerative capacity of mouse skeletal muscle cells exposed to saturated fat and inflammation.

Saini Amarjit A Sharples Adam P AP Al-Shanti Nasser N Stewart Claire E CE

Biogerontology 20161118 1

Sarcopenic obesity is characterised by high fat mass, low muscle mass and an elevated inflammatory environmental milieu. We therefore investigated the effects of elevated inflammatory cytokine TNF-α (aging/obesity) and saturated fatty acid, palmitate (obesity) on skeletal muscle cells in the presence/absence of EPA, a-3 polyunsaturated fatty acid with proposed anti-inflammatory, anti-obesity activities. In the present study we show that palmitate was lipotoxic, inducing high levels of cell death ...[more]

PMID: 27864687

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Project description:PurposeTo investigate the effects of endurance training on the content of ω-3 polyunsaturated fatty acids (PUFAs) and their distribution among lipid classes in skeletal muscle in middle aged, high-fat diet fed rats.MethodThirty 10-month old male Sprague Dawley (SD) rats were assigned to four groups. Two groups of rats remained sedentary and were fed chow diet (C group), or high-fat diet (H group), respectively. The other two groups of rats were subjected to endurance training while maintaining their chow diet (EC group), or high-fat diet (EH group). After 16 weeks endurance training and/or diet intervention, the content of ω-3 PUFAs and ω-3 PUFA-containing lipids in rat soleus muscle were analyzed by lipidomics.ResultsRats fed a high-fat diet exhibited decreased overall amount of ω-3 PUFAs in soleus muscle, while endurance training preserved the total amount of ω-3 PUFAs. Both the endurance training and high-fat diet alone changed the profiles of ω-3 PUFAs in different lipid classes. Specifically, the amount of triacylglycerol (TG), lysophosphatidylcholine (LPC), phosphatidylcholine (PC), and phosphatidylglycerol (PG) containing ω-3 PUFAs in soleus muscle was increased by endurance training, but the amount of lysophosphatidylenthanol (LPE), lysophosphatidylinositol (LPI), lysophosphatidylserine (LPS), cardiolipin (CL), phosphatidic acid (PA), and phosphatidylinositol (PI) was decreased. The high-fat diet induced a decrease of ω-3 PUFAs in TG, LPE, LPS, CL, platelet activating factor (PAF), PC, phosphatidylethanolamine (PE), and phosphatidylserine (PS), and an increase in LPC, LPI, PA, and PG. In addition, the effects of the endurance training on ω-3 PUFAs in skeletal muscle was also evident in high-fat diets fed rats, which counteracts the profiling changes caused by high-fat diet feeding.ConclusionThe beneficial effects of endurance training on skeletal muscle may be achieved to some extent through recovering the content of ω-3 PUFAs that has been decreased by high-fat diet feeding.

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Omega-3 fatty acid EPA improves regenerative capacity of mouse skeletal muscle cells exposed to saturated fat and inflammation.

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Omega-3 fatty acid EPA improves regenerative capacity of mouse skeletal muscle cells exposed to saturated fat and inflammation.

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