Effects of Eicosapentaenoic Acid and Docosahexaenoic Acid on Mitochondrial DNA Replication and PGC-1α Gene Expression in C2C12Muscle Cells

Lee, Mak-Soon; Shin, Yoonjin; Moon, Sohee; Kim, Seunghae; Kim, Yangha

doi:10.3746/pnf.2016.21.4.317

Cited by 28 publications

(26 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…19 Consistently, DHA was reported to upregulate mRNA levels of Pgc1α and stimulate PGC1α promoter activity in a doseand time-dependent manner in C2C12 muscle cells. 20 These results suggest that the anti-hepatosteatotic effect of DHA in our NAFLD model is partly mediated by the modulation of mitochondrial biogenesis and promotion of TAG export but not the reduction of hepatic lipogenesis. The protective effect of DHA on hepatic steatosis in vivo was also supported by in vitro data.…”

Section: Discussionmentioning

confidence: 52%

DHA Protects Against Hepatic Steatosis by Activating Sirt1 in a High Fat Diet-Induced Nonalcoholic Fatty Liver Disease Mouse Model

Luo

Sun

et al. 2020

DMSO

View full text Add to dashboard Cite

Docosahexaenoic acid (DHA; C22; n-3) shows beneficial effects on Non-alcoholic fatty liver disease (NAFLD). Deacetylase Sirtuin1 (Sirt1) was reported to increase energy metabolism and decrease lipogenesis. Here, we investigated whether DHA plays a role in protecting against hepatic steatosis via Sirt1. Main Methods: Both in vivo and in vitro hepatic steatosis models were used: diet-induced obesity (DIO) model (middle-aged C57BL/6 mice fed a high-fat diet (HFD)) and palmitic acid (PA)-induced lipid accumulation cell model (HepG2 cells). Key Findings: In DIO mice, treatment with DHA (gavage supplementation) for 8 weeks not only inhibited the lipid accumulation, but also increased fatty acids (FA) oxidation and induced triglyceride export in liver. These changes were accompanied by attenuation of inflammation. Moreover, DHA reversed the HFD-induced reduction of Sirt1 in liver. Interestingly, the beneficial effects of DHA were reversed by lentivirus-mediated Sirt1 knockdown, accompanied with increased expression of markers of lipogenesis, inflammation and reduced FA oxidation. In HepG2 cells, DHA prevented the accumulation of PA-induced lipid droplets, the decrease of FA oxidation and the reduction of Sirt1 level. Inhibition of Sirt1 by sirtinol partially reversed the beneficial effects of DHA on PA-treated cells. Significance: DHA alleviated hepatic steatosis and reduced inflammation of liver in obese middle-aged mice by mechanisms involving Sirt1 activation.

show abstract

Section: Discussionmentioning

confidence: 52%

DHA Protects Against Hepatic Steatosis by Activating Sirt1 in a High Fat Diet-Induced Nonalcoholic Fatty Liver Disease Mouse Model

Luo

Sun

et al. 2020

DMSO

View full text Add to dashboard Cite

show abstract

“…It was reported that the n − 3 PUFAs could cause higher oxidation levels of mitochondrial fatty acids in the myocardium ( 19 – 22 ). EPA and DHA individually increase mitochondrial biosynthesis in skeletal muscle stem cells ( 23 – 25 ). Therefore, we hypothesize that EPA and DHA treatment on myofibroblasts (C2C12 cells) may affect the myogenesis and adipogenesis via metabolic changes in mitochondria.…”

Section: Introductionmentioning

confidence: 99%

Effect of Eicosapentaenoic Acid and Docosahexaenoic Acid on Myogenesis and Mitochondrial Biosynthesis during Murine Skeletal Muscle Cell Differentiation

Hsueh¹,

Baum²,

Huang³

2018

Front. Nutr.

View full text Add to dashboard Cite

Polyunsaturated fatty acids are important nutrients for human health, especially omega-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which have been found to play positive roles in the prevention of various diseases. However, previous studies have reported that excessive omega-3 fatty acids supplement during pregnancy caused side effects such as slower neural transmission times and postnatal growth restriction. In this study, we investigated the effect of EPA and DHA on mitochondrial function and gene expression in C2C12 myoblasts during skeletal muscle differentiation. C2C12 myoblasts were cultured to confluency and then treated with differentiation medium that contained fatty acids (50-µM EPA and DHA). After 72 h of myogenic differentiation, mRNA was collected, and gene expression was analyzed by real-time PCR. Microscopy was used to examine cell morphology following treatment with fatty acids. The effect of EPA and DHA on cellular oxygen consumption was measured using a Seahorse XF24 Analyzer. Cells treated with fatty acids had fewer myotubes formed (P ≤ 0.05) compared with control cells. The expression of the genes related to myogenesis was significantly lower (P ≤ 0.05) in cells treated with fatty acids, compared with control cells. Genes associated with adipogenesis had higher (P ≤ 0.05) expression after treatment with fatty acids. Also, the mitochondrial biogenesis decreased with lower (P ≤ 0.05) gene expression and lower (P ≤ 0.05) mtDNA/nDNA ratio in cells treated with fatty acids compared with control cells. However, the expression of genes related to peroxisome biosynthesis was higher (P ≤ 0.05) in cells treated with fatty acids. Moreover, fatty-acid treatment reduced (P ≤ 0.05) oxygen consumption rate under oligomycin-inhibited (reflecting proton leak) and uncoupled conditions. Our data imply that fatty acids might reduce myogenesis and increase adipogenesis in myotube formation. Fatty acids may also decrease cell metabolism by reducing mitochondrial biogenesis as well as respiration rate. This study suggests that the maternal overdosage of EPA and DHA may influence fetal muscle development, increase intramuscular adipose tissue deposition in offspring, and have a long-term effect on the development of metabolic diseases such as obesity and diabetes in adult offspring.

show abstract

“…Like PPARs, the peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1α) is also capable of repressing the transcriptional activity of NF-kB lowering inflammation in muscle cells [ 90 ]. In differentiated C2C12 myotubes, n-3 PUFAs have been found to increase the expression of PGC-1α in a dose and time dependent manner with 50 μM for 24 h having the greatest effect [ 91 ]. PGC-1α is also indirectly involved in regulating the expression of mitochondrial DNA (mtDNA) by increasing the transcription of mitochondrial transcription factor A (Tfam) and nuclear respiratory factor 1 (NRF1) [ 92 ].…”

Section: The Beneficial Effects Of N-3 Pufas In Skeletal Musclementioning

confidence: 99%

“…PGC-1α is also indirectly involved in regulating the expression of mitochondrial DNA (mtDNA) by increasing the transcription of mitochondrial transcription factor A (Tfam) and nuclear respiratory factor 1 (NRF1) [ 92 ]. In fully formed myotubes, the expression of both Tfam and NRF1 have been shown to increase following both EPA and DHA treatment [ 91 ]. Moreover, overexpressing PGC-1α in C2C12 cells has been shown to promote differentiation and increase the expression of MyoD and Myogenin, however, it remains to be seen whether n-3 PUFAs can elicit similar responses in both PGC-1α and MRF expression during differentiation [ 93 ].…”

Section: The Beneficial Effects Of N-3 Pufas In Skeletal Musclementioning

confidence: 99%

Potential Roles of n-3 PUFAs during Skeletal Muscle Growth and Regeneration

2018

View full text Add to dashboard Cite

Omega-3 polyunsaturated fatty acids (n-3 PUFAs), which are commonly found in fish oil supplements, are known to possess anti-inflammatory properties and more recently alter skeletal muscle function. In this review, we discuss novel findings related to how n-3 PUFAs modulate molecular signaling responsible for growth and hypertrophy as well as the activity of muscle stem cells. Muscle stem cells commonly known as satellite cells, are primarily responsible for driving the skeletal muscle repair process to potentially damaging stimuli, such as mechanical stress elicited by exercise contraction. To date, there is a paucity of human investigations related to the effects of n-3 PUFAs on satellite cell content and activity. Based on current in vitro investigations, this review focuses on novel mechanisms linking n-3 PUFA’s to satellite cell activity and how they may improve muscle repair. Understanding the role of n-3 PUFAs during muscle growth and regeneration in association with exercise could lead to the development of novel supplementation strategies that increase muscle mass and strength, therefore possibly reducing the burden of muscle wasting with age.

show abstract

Effects of Eicosapentaenoic Acid and Docosahexaenoic Acid on Mitochondrial DNA Replication and PGC-1α Gene Expression in C₂C₁₂Muscle Cells

Cited by 28 publications

References 28 publications

<p>DHA Protects Against Hepatic Steatosis by Activating Sirt1 in a High Fat Diet-Induced Nonalcoholic Fatty Liver Disease Mouse Model</p>

<p>DHA Protects Against Hepatic Steatosis by Activating Sirt1 in a High Fat Diet-Induced Nonalcoholic Fatty Liver Disease Mouse Model</p>

Effect of Eicosapentaenoic Acid and Docosahexaenoic Acid on Myogenesis and Mitochondrial Biosynthesis during Murine Skeletal Muscle Cell Differentiation

Potential Roles of n-3 PUFAs during Skeletal Muscle Growth and Regeneration

Contact Info

Product

Resources

About