Repository of Research and Investigative Information

Repository of Research and Investigative Information

Ilam University of Medical Sciences

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

Mon Jun 17 02:24:44 2024

(2015) TNF-α knockdown alleviates palmitate-induced insulin resistance in C2C12 skeletal muscle cells. Biochemical and Biophysical Research Communications. pp. 977-982. ISSN 0006291X (ISSN)

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Insulin resistance is a cardinal feature of Type 2 Diabetes (T2D), which accompanied by lipid accumulation and TNF-α overexpression in skeletal muscle. The role of TNF-α in palmitate-induced insulin resistance remained to be elucidated. Here, we assessed effects of TNF-α knockdown on the components of insulin signaling pathway (IRS-1 and Akt) in palmitate-induced insulin resistant C2C12 skeletal muscle cells. To reduce TNF-α expression, C2C12 cells were transduced with TNF-α-shRNA lentiviral particles. Afterwards, the protein expression of TNF-α, IRS-1, and Akt, as well as phosphorylation levels of IRS-1 and Akt were evaluated by western blot. We also measured insulin-stimulated glucose uptake in the presence and absence of palmitate. TNF-α protein expression in C2C12 cells significantly increased by treatment with 0.75 mM palmitate (P < 0.05). In TNF-α knockdown cells, the protein expression level of TNF-α was significantly decreased by almost 70 (P < 0.01) compared with the control cells. Our results also revealed that, in control cells, palmitate treatment significantly reduced the insulin-induced phosphorylations of IRS-1 (Tyr632) and Akt (Ser473) by 60 and 66 (P < 0.01), respectively. Interestingly, these phosphorylations, even in the presence of palmitate, were not significantly reduced in TNF-α knockdown cells with respect to the untreated control cells (P > 0.05). Furthermore, palmitate significantly reduced insulin-dependent glucose uptake in control cells, however, it was not able to reduce insulin-stimulated glucose uptake in TNF-α knockdown cells in comparison with the untreated control cells (P < 0.01). These findings indicated that TNF-α down-regulation maintains insulin sensitivity, even in the presence of palmitate, therefore, TNF-α inhibition could be a good strategy for the treatment of palmitate-induced insulin resistance. © 2015 Elsevier Inc. All rights reserved.

Item Type: Article
Keywords: Insulin resistance Knockdown Palmitate Short hairpin RNA TNF-α palmitic acid tumor necrosis factor alpha animal cell line drug effects gene silencing genetics metabolism mouse phosphorylation physiology skeletal muscle Western blotting Animals Blotting, Western Gene Knockdown Techniques Mice Muscle, Skeletal Tumor Necrosis Factor-alpha
Page Range: pp. 977-982
Journal or Publication Title: Biochemical and Biophysical Research Communications
Journal Index: Scopus
Volume: 460
Number: 4
Identification Number:
ISSN: 0006291X (ISSN)
Depositing User: مهندس مهدی شریفی

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