Fatty acid-induced NF-κB activation and insulin resistance in skeletal muscle are chain length dependent

2009 ◽  
Vol 296 (1) ◽  
pp. E114-E120 ◽  
Author(s):  
Pascal P. H. Hommelberg ◽  
Jogchum Plat ◽  
Ramon C. J. Langen ◽  
Annemie M. W. J. Schols ◽  
Ronald P. Mensink
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Fatty Acid ◽  
Chain Length ◽  
Transcriptional Activity ◽  
Muscle Cells ◽  
Binding Activity ◽  
Skeletal Muscle Cells ◽  
Glut4 Translocation ◽  
L6 Cells

The saturated fatty acid (SFA) palmitate induces insulin resistance in cultured skeletal muscle cells, which may be related to NF-κB activation. The aim of this study was to evaluate whether other SFAs also exert these effects on skeletal muscle and whether these relate to chain length. Therefore, we incubated L6 and C2C12 skeletal muscle cells with four different fatty acids, caprylate (C8:0), laurate (C12:0), palmitate (C16:0), and stearate (C18:0), to study effects on GLUT4 translocation, deoxyglucose uptake, and NF-κB activation. Incubation of L6 cells with the long-chain FAs C16:0 and C18:0 reduced insulin-stimulated GLUT4 translocation and deoxyglucose uptake, whereas L6 cells incubated with the medium-chain FAs C8:0 and C12:0 remained insulin sensitive. Besides increasing NF-κB DNA binding activity in both L6 and C2C12 cells, C16:0 also induced NF-κB transcriptional activity. C18:0 showed comparable effects, whereas the SFAs with shorter chain lengths were not able to elevate NF-κB transcriptional activity. Collectively, these results demonstrate that SFA-induced NF-κB activation coincides with insulin resistance and depends on FA chain length.

A Novel Partial PPARγ Agonist Has Weaker Lipogenic Effect in Adipocytes and Stimulates GLUT4 Translocation in Skeletal Muscle Cells via AMPK-Dependent Signaling

Pharmacology ◽  
2021 ◽  
pp. 1-12
Author(s):  
Bhavimani Guru ◽  
Akhilesh K. Tamrakar ◽  
Subhankar P. Mandal ◽  
Prashantha B.R. Kumar ◽  
Aditya Sharma ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Molecular Docking ◽  
Md Simulation ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Dependent Manner ◽  
Glut4 Translocation ◽  
Binding Interactions ◽  
Pparγ Agonists

<b><i>Introduction:</i></b> Peroxisome proliferator-activated receptor gamma (PPARγ) agonists are highly effective in treating insulin resistance. However, associated side effects such as weight gain due to increase in adipogenesis and lipogenesis hinder their clinical use. The aim of the study was to design and synthesize novel partial PPARγ agonists with weaker lipogenic effect in adipocytes and enhanced glucose transporter 4 (GLUT4) translocation stimulatory effect in skeletal muscle cells. <b><i>Methods:</i></b> Novel partial PPARγ agonists (GS1, GS2, and GS3) were designed and screened to predict their binding interactions with PPARγ by molecular docking. The stability of the docked ligand-PPARγ complex was studied by molecular dynamics (MD) simulation. The cytotoxicity of synthesized compounds was tested in 3T3-L1 adipocytes and L6 myoblasts by MTT assay. The lipogenic effect was investigated in 3T3-L1 adipocytes using oil red O staining and GLUT4 translocation stimulatory effect in L6-GLUT4<i>myc</i> myotubes by an antibody-coupled colorimetric assay. <b><i>Results:</i></b> The molecular docking showed the binding interactions between designed agonists and PPARγ. MD simulation demonstrated good stability between the GS2-PPARγ complex. GS2 and GS3 did not show any significant effect on cell viability up to 80 or 100 μM concentration. Pioglitazone treatment significantly increased intracellular lipid accumulation in adipocytes compared to control. However, this effect was significantly less in GS2- and GS3-treated conditions compared to pioglitazone at 10 μM concentration, indicating weaker lipogenic effect. Furthermore, GS2 significantly stimulated GLUT4 translocation to the plasma membrane in a dose-dependent manner via the AMPK-dependent signaling pathway in skeletal muscle cells. <b><i>Conclusion:</i></b> GS2 may be a promising therapeutic agent for the treatment of insulin resistance and type 2 diabetes mellitus without adiposity.

scholarly journals Erratum to: Trans Fatty Acid-Induced NF-κB Activation Does Not Induce Insulin Resistance in Cultured Murine Skeletal Muscle Cells

Lipids ◽  
2010 ◽  
Vol 45 (5) ◽  
pp. 463-464
Author(s):  
Pascal P. H. Hommelberg ◽  
Ramon C. J. Langen ◽  
Annemie M. W. J. Schols ◽  
Anon L. M. van Essen ◽  
Frank J. M. Snepvangers ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Fatty Acid ◽  
Trans Fatty Acid ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Induce Insulin Resistance ◽  
Murine Skeletal Muscle

Trans Fatty Acid-Induced NF-κB Activation Does Not Induce Insulin Resistance in Cultured Murine Skeletal Muscle Cells

Lipids ◽  
2010 ◽  
Vol 45 (3) ◽  
pp. 285-290 ◽  
Author(s):  
Pascal P. H. Hommelberg ◽  
Ramon C. J. Langen ◽  
Annemie M. W. J. Schols ◽  
Anon L. M. van Essen ◽  
Frank J. M. Snepvangers ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Fatty Acid ◽  
Trans Fatty Acid ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Induce Insulin Resistance ◽  
Murine Skeletal Muscle

Clove and Its Active Compound Attenuate Free Fatty Acid-Mediated Insulin Resistance in Skeletal Muscle Cells and in Mice

2017 ◽  
Vol 20 (4) ◽  
pp. 335-344 ◽  
Author(s):  
Safina Ghaffar ◽  
Shabbir Khan Afridi ◽  
Meha Fatima Aftab ◽  
Munazza Murtaza ◽  
Rahman M. Hafizur ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Active Compound ◽  
Muscle Cells ◽  
Skeletal Muscle Cells

4-Hydroxyisoleucine ameliorates fatty acid-induced insulin resistance and inflammatory response in skeletal muscle cells

2014 ◽  
Vol 395 (1-2) ◽  
pp. 51-60 ◽  
Author(s):  
Chandan Kumar Maurya ◽  
Rohit Singh ◽  
Natasha Jaiswal ◽  
K. Venkateswarlu ◽  
Tadigoppula Narender ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Fatty Acid ◽  
Inflammatory Response ◽  
Muscle Cells ◽  
Skeletal Muscle Cells

scholarly journals Anthocyanins from Aristotelia chilensis Prevent Olanzapine-Induced Hepatic-Lipid Accumulation but Not Insulin Resistance in Skeletal Muscle Cells

Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6149
Author(s):  
Andrea del Campo ◽  
Catalina Salamanca ◽  
Angelo Fajardo ◽  
Francisco Díaz-Castro ◽  
Catalina Bustos ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Metabolic Syndrome ◽  
Lipid Accumulation ◽  
Muscle Cells ◽  
Liver Cells ◽  
Skeletal Muscle Cells ◽  
Dietary Polyphenols ◽  
L6 Cells ◽  
Aristotelia Chilensis

Type 2 diabetes and obesity are major problems worldwide and dietary polyphenols have shown efficacy to ameliorate signs of these diseases. Anthocyanins from berries display potent antioxidants and protect against weight gain and insulin resistance in different models of diet-induced metabolic syndrome. Olanzapine is known to induce an accelerated form of metabolic syndrome. Due to the aforementioned, we evaluated whether delphinidin-3,5-O-diglucoside (DG) and delphinidin-3-O-sambubioside-5-O-glucoside (DS), two potent antidiabetic anthocyanins isolated from Aristotelia chilensis fruit, could prevent olanzapine-induced steatosis and insulin resistance in liver and skeletal muscle cells, respectively. HepG2 liver cells and L6 skeletal muscle cells were co-incubated with DG 50 μg/mL or DS 50 μg/mL plus olanzapine 50 μg/mL. Lipid accumulation was determined in HepG2 cells while the expression of p-Akt as a key regulator of the insulin-activated signaling pathways, mitochondrial function, and glucose uptake was assessed in L6 cells. DS and DG prevented olanzapine-induced lipid accumulation in liver cells. However, insulin signaling impairment induced by olanzapine in L6 cells was not rescued by DS and DG. Thus, anthocyanins modulate lipid metabolism, which is a relevant factor in hepatic tissue, but do not significantly influence skeletal muscle, where a potent antioxidant effect of olanzapine was found.

scholarly journals Activation of Peroxisome Proliferator-Activated Receptor-δ by GW501516 Prevents Fatty Acid-Induced Nuclear Factor-κB Activation and Insulin Resistance in Skeletal Muscle Cells

Endocrinology ◽  
2010 ◽  
Vol 151 (4) ◽  
pp. 1560-1569 ◽  
Author(s):  
Teresa Coll ◽  
David Álvarez-Guardia ◽  
Emma Barroso ◽  
Anna Maria Gómez-Foix ◽  
Xavier Palomer ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Carnitine Palmitoyltransferase 1

Elevated plasma free fatty acids cause insulin resistance in skeletal muscle through the activation of a chronic inflammatory process. This process involves nuclear factor (NF)-κB activation as a result of diacylglycerol (DAG) accumulation and subsequent protein kinase Cθ (PKCθ) phosphorylation. At present, it is unknown whether peroxisome proliferator-activated receptor-δ (PPARδ) activation prevents fatty acid-induced inflammation and insulin resistance in skeletal muscle cells. In C2C12 skeletal muscle cells, the PPARδ agonist GW501516 prevented phosphorylation of insulin receptor substrate-1 at Ser307 and the inhibition of insulin-stimulated Akt phosphorylation caused by exposure to the saturated fatty acid palmitate. This latter effect was reversed by the PPARδ antagonist GSK0660. Treatment with the PPARδ agonist enhanced the expression of two well known PPARδ target genes involved in fatty acid oxidation, carnitine palmitoyltransferase-1 and pyruvate dehydrogenase kinase 4 and increased the phosphorylation of AMP-activated protein kinase, preventing the reduction in fatty acid oxidation caused by palmitate exposure. In agreement with these changes, GW501516 treatment reversed the increase in DAG and PKCθ activation caused by palmitate. These effects were abolished in the presence of the carnitine palmitoyltransferase-1 inhibitor etomoxir, thereby indicating that increased fatty acid oxidation was involved in the changes observed. Consistent with these findings, PPARδ activation by GW501516 blocked palmitate-induced NF-κB DNA-binding activity. Likewise, drug treatment inhibited the increase in IL-6 expression caused by palmitate in C2C12 and human skeletal muscle cells as well as the protein secretion of this cytokine. These findings indicate that PPARδ attenuates fatty acid-induced NF-κB activation and the subsequent development of insulin resistance in skeletal muscle cells by reducing DAG accumulation. Our results point to PPARδ activation as a pharmacological target to prevent insulin resistance.

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