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Puerarin attenuates palmitate-induced mitochondrial dysfunction, impaired mitophagy and inflammation in L6 myotubes.

Abstract：

AIMS:High level of saturated fatty acids leads to mitochondrial dysfunction and inflammation in the development of insulin resistance in skeletal muscle. We recently found that puerarin improved impaired insulin signaling in skeletal muscle in diabetic animals and in myotubes in vitro. However, whether puerarin can act directly on muscle cells to alleviate lipid-induced mitochondrial dysfunction and inflammation remains obscure. This study was conducted to analyze the attributive properties of puerarin against mitochondrial dysfunction and inflammation in skeletal muscle cells with insulin resistance. MAIN METHODS:The effects of puerarin on mitochondrial biogenesis, oxidative phosphorylation, dynamics of fusion, fission and mitophagy, oxidative stress, as well as inflammatory response and insulin sensitivity in L6 myotubes treated with palmitate were examined. KEY FINDINGS:Puerarin pretreatment improve insulin sensitivity and prevented muscle cells from palmitate-induced mitochondrial dysfunction manifested by the increases of complex I activity, mitochondrial membrane potential and ATP generation, and the decrease of reactive oxygen species (ROS) production. Augmented expression of genes involved in mitochondrial biogenesis, oxidative phosphorylation, and the detoxification of ROS were also observed upon puerarin supplementation. Moreover, puerarin modulated mitochondrial fusion and fission, and rescued palmitate-impaired mitophagy via phosphatase and tensin homolog-induced putative kinase 1(PINK1)/Parkin pathway. In addition, puerarin attenuated palmitate-induced inflammation through the inhibition of toll-like receptor 4/nuclear factor-κB signaling pathway. SIGNIFICANCE:Our findings indicated that puerarin could act directly on muscle cells to attenuate palmitate-induced mitochondrial dysfunction, impaired mitophagy and inflammatory response, thereby contributing to the improvement of insulin sensitivity.

journal_name

Life Sci

journal_title

Life sciences

authors

Chen X,Yi L,Song S,Wang L,Liang Q,Wang Y,Wu Y,Gao Q

doi

10.1016/j.lfs.2018.05.041

subject

Has Abstract

pub_date

2018-08-01 00:00:00

pages

84-92

eissn

0024-3205

issn

1879-0631

pii

S0024-3205(18)30309-6

journal_volume

206

pub_type

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Puerarin attenuates palmitate-induced mitochondrial dysfunction, impaired mitophagy and inflammation in L6 myotubes.