TNF-α knockdown alleviates palmitate-induced insulin resistance in C2C12 skeletal muscle cells

Haghani, Karimeh; Pashaei, Somayeh; Vakili, Sanaz; Taheripak, Gholamreza; Bakhtiyari, Salar

doi:10.1016/j.bbrc.2015.03.137

Cited by 26 publications

(28 citation statements)

References 49 publications

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“…Thus far, studies of skeletal muscle have predominantly focused on defects in orchestrating insulin signals during obesity. Although it is recognized that inflammation is triggered by lipid-laden adipose tissue under obese conditions, recent studies have demonstrated that skeletal muscle also secretes pro-inflammatory cytokines, such as tumour necrosis factor alpha (TNF-a), in response to elevated FFA levels [30]. However, those findings were restricted to investigations of the mechanisms underlying insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

Conditioned media from human palatine tonsil mesenchymal stem cells regulates the interaction between myotubes and fibroblasts by IL‐1Ra activity

Cho

Park

Kim

et al. 2016

J Cellular Molecular Medi

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Saturated free fatty acids (FFAs) act as lipid mediators and induce insulin resistance in skeletal muscle. Specifically, in obesity‐related diseases such as type 2 diabetes, FFAs directly reduce insulin sensitivity and glucose uptake in skeletal muscle. However, the knowledge of how FFAs mediate inflammation and subsequent tissue disorders, including fibrosis in skeletal muscle, is limited. FFAs are a natural ligand for toll‐like receptor 2 (TLR2) and TLR4, and induce chronic low‐grade inflammation that directly stimulates skeletal muscle tissue. However, persistent inflammatory stimulation in tissues could induce pro‐fibrogenic processes that ultimately lead to perturbation of the tissue architecture and dysfunction. Therefore, blocking the link between inflammatory primed skeletal muscle tissue and connective tissue might be an efficient therapeutic option for treating obesity‐induced muscle inactivity. In this study, we investigated the impact of conditioned medium obtained from human palatine tonsil‐derived mesenchymal stem cells (T‐MSCs) on the interaction between skeletal muscle cells stimulated with palmitic acid (PA) and fibroblasts. We found that PA‐treated skeletal muscle cells actively secreted interleukin‐1β (IL‐1β) and augmented the migration, proliferation and expression of fibronectin in L929 fibroblasts. Furthermore, T‐CM inhibited the skeletal muscle cell‐derived pro‐fibrogenic effect via the production of the interleukin‐1 receptor antagonist (IL‐1Ra), which is an inhibitor of IL‐1 signalling. Taken together, our data provide novel insights into the therapeutic potential of T‐MSC‐mediated therapy for the treatment of pathophysiological processes that occur in skeletal muscle tissues under chronic inflammatory conditions.

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Section: Discussionmentioning

confidence: 99%

Conditioned media from human palatine tonsil mesenchymal stem cells regulates the interaction between myotubes and fibroblasts by IL‐1Ra activity

Cho

Park

Kim

et al. 2016

J Cellular Molecular Medi

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“…In C2C12 muscle cells, palmitate, an activator of PKC-, caused a time-dependent increase in TNF-␣ expression (23). shRNA-mediated knockdown of TNF-␣ preserved insulin-stimulated Akt phosphorylation in the presence of palmitate (23). Therefore, a reduction in TNF-␣ mRNA levels shown here in SkM PKCKO mice following HFD suggests that PKC-contributes to skeletal muscle inflammation and insulin resistance in a lipotoxic state.…”

Section: Discussionmentioning

confidence: 69%

“…SkM PKCKO mice on a HFD had significantly lower muscle TNF-␣ transcript expression, suggesting that the inflammatory response that typically accompanies IMCL accumulation was reduced (20,53). In C2C12 muscle cells, palmitate, an activator of PKC-, caused a time-dependent increase in TNF-␣ expression (23). shRNA-mediated knockdown of TNF-␣ preserved insulin-stimulated Akt phosphorylation in the presence of palmitate (23).…”

Section: Discussionmentioning

confidence: 99%

Mice lacking PKC-θ in skeletal muscle have reduced intramyocellular lipid accumulation and increased insulin responsiveness in skeletal muscle

Peck

Huot

Renzi

et al. 2018

American Journal of Physiology-Regulatory, Integrative and Comp

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Protein kinase C-θ (PKC-θ) is a lipid-sensitive molecule associated with lipid-induced insulin resistance in skeletal muscle. Rodent models have not cohesively supported that PKC-θ impairs insulin responsiveness in skeletal muscle. The purpose of this study was to generate mice that lack PKC-θ in skeletal muscle and determine how lipid accumulation and insulin responsiveness are affected in that tissue. Mice lacking PKC-θ in skeletal muscle (SkM) and controls (SkM) were placed on a regular diet (RD) or high-fat diet (HFD) for 15 wk, followed by determination of food intake, fasting glucose levels, lipid accumulation, and insulin responsiveness. There were no differences between SkM and SkM mice on a RD. SkM mice on a HFD gained less weight from 10 through 15 wk of dietary intervention ( P < 0.05). This was likely due to less caloric consumption ( P = 0.0183) and fewer calories from fat ( P < 0.001) compared with SkM mice on a HFD. Intramyocellular lipid accumulation ( P < 0.0001), fatty acid binding protein 4, and TNF-α mRNA levels ( P < 0.05) were markedly reduced in SkM compared with SkM mice on a HFD. As a result, fasting hyperglycemia was mitigated and insulin responsiveness, as indicated by Akt phosphorylation, was maintained in SkM on a HFD. Liver lipid accumulation was not affected by genotype, suggesting the deletion of PKC-θ from skeletal muscle has a tissue-specific effect. PKC-θ is a regulator of lipid-induced insulin resistance in skeletal muscle. However, the effects of this mutation may be tissue specific. Further work is warranted to comprehensively evaluated whole body metabolic responses in this model.

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“…In a study reported by Deng et al () on neutralizing the lipid‐dependent insulin resistance through phytopolyphenols in C2C12 cells, it was showed that treatment with EGCG and curcumin (a bioactive compound found in turmeric) could increase phosphorylation of 307 Serine and Akt in muscle cells, and subsequently, could affect the IRS1. Karimfar et al () and Haghani et al () demonstrated that although both rosiglitazone and EGCG could exert some degree of antidiabetic activity via increasing insulin sensitivity (through different molecular‐cellular mechanisms), only rosiglitazone (but not EGCG) could counteract downregulation of PGC‐1α expression.…”

Section: Discussionmentioning

confidence: 99%

“…This method was used to investigate the effects of rosiglitazone and EGCG on insulin‐resistant cells induced with palmitate. The protein extracts of C2C12 cells were obtained by homogenizing in a radioimmunoprecipitation buffer (Haghani et al, ) (50 mM Tris–HCL, 1% Triton‐x100, 0.2% sodium dodecyl carbonate, 1 mM Na‐ethylenediaminetetraacetic acid [EDTA], and 1 mM phenylmethane sulfonyl fluoride [PMSF]) and measuring the protein concentration using the Bradford method (Bradford, ). An amount of 20–30 μg of the protein extract was electrophoresed on an sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS‐PAGE) gel and the cells were then transferred from the gel to the nitrocellulose membrane before being incubated in 2% bovine serum albumin (BSA) solution for one night (4 °C).…”

Section: Methodsmentioning

confidence: 99%

The Phosphorylation of IRS1^S307 and Akt^S473 Molecules in Insulin‐Resistant C2C12 Cells Induced with Palmitate Is Influenced by Epigallocatechin Gallate from Green Tea

Bakhtiyari

Zaherara

Haghani

et al. 2019

Lipids

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In the current investigation, the effect of epigallocatechin gallate (EGCG) on the phosphorylation of IRS1S307 and AktS473 molecules in insulin‐resistant C2C12 muscle cells induced with palmitate was studied and compared with the effect of the antidiabetic drug, rosiglitazone. C2C12 myoblasts were cultured in Dulbecco's modified Eagle's medium and differentiated into myotubes using horse serum and the creatine kinase test was used to confirm their differentiation. The treatment of C2C12 myotubes was carried out with palmitate, where albumin was used as the conjugator. The Western blot technique was used to check the useful phosphorylation of IRS1S307 and AktS473 in C2C12 myotubes, in the presence or absence of palmitate. There was a significant (p < 0.00) and linear increase in the activity of creatine kinase over time (0 to 96 h after differentiation) with everyday myoblast formation. While neither EGCG nor rosiglitazone showed a significant (p > 0.05) effect on palmitate content during 96 h of incubation of IRS1S307, EGCG alone or combined with rosiglitazone increased the phosphorylation of AktS473, leading to the increase of glucose uptake into C2C12 cells. Thus, it can be concluded that EGCG alone or in combination with rosiglitazone may show some therapeutic effects for the prevention or treatment of Type 2 diabetes owing to its substantial effect on increasing the phosphorylation of AktS473 and the subsequent glucose uptake into the cells.

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TNF-α knockdown alleviates palmitate-induced insulin resistance in C2C12 skeletal muscle cells

Cited by 26 publications

References 49 publications

Conditioned media from human palatine tonsil mesenchymal stem cells regulates the interaction between myotubes and fibroblasts by IL‐1Ra activity

Conditioned media from human palatine tonsil mesenchymal stem cells regulates the interaction between myotubes and fibroblasts by IL‐1Ra activity

Mice lacking PKC-θ in skeletal muscle have reduced intramyocellular lipid accumulation and increased insulin responsiveness in skeletal muscle

The Phosphorylation of IRS1^S307 and Akt^S473 Molecules in Insulin‐Resistant C2C12 Cells Induced with Palmitate Is Influenced by Epigallocatechin Gallate from Green Tea

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TNF-α knockdown alleviates palmitate-induced insulin resistance in C2C12 skeletal muscle cells

Cited by 26 publications

References 49 publications

Conditioned media from human palatine tonsil mesenchymal stem cells regulates the interaction between myotubes and fibroblasts by IL‐1Ra activity

Conditioned media from human palatine tonsil mesenchymal stem cells regulates the interaction between myotubes and fibroblasts by IL‐1Ra activity

Mice lacking PKC-θ in skeletal muscle have reduced intramyocellular lipid accumulation and increased insulin responsiveness in skeletal muscle

The Phosphorylation of IRS1S307 and AktS473 Molecules in Insulin‐Resistant C2C12 Cells Induced with Palmitate Is Influenced by Epigallocatechin Gallate from Green Tea

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The Phosphorylation of IRS1^S307 and Akt^S473 Molecules in Insulin‐Resistant C2C12 Cells Induced with Palmitate Is Influenced by Epigallocatechin Gallate from Green Tea