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J Food Drug Anal. 2018 Jul;26(3):1066-1074. doi: 10.1016/j.jfda.2018.01.006. Epub 2018 Feb 3.

Resveratrol protects muscle cells against palmitate-induced cellular senescence and insulin resistance through ameliorating autophagic flux.

Author information

1
Department of Life Sciences, National Cheng Kung University, Tainan, Taiwan.
2
Department of Physical Education, National Taiwan Normal University, Taipei, Taiwan.
3
Department of Life Sciences, National Cheng Kung University, Tainan, Taiwan; School of Food Safety, Taipei Medical University, Taipei, Taiwan.
4
Department of Life Sciences, National Cheng Kung University, Tainan, Taiwan. Electronic address: sjchang@mail.ncku.edu.tw.

Abstract

Skeletal muscle, a highly metabolic tissue, is particularly vulnerable to increased levels of saturated free fatty acids (FFAs). The role of autophagy in saturated FFAs-induced cellular senescence and insulin resistance in skeletal muscle remains unclear. Therefore, the present study was aimed to explore autophagic flux in cellular senescence and insulin resistance induced by palmitate in muscle cells, and whether resveratrol limited these responses. Our results showed that palmitate induced cellular senescence in both myoblasts and myotubes. In addition, palmitate delayed differentiation in myoblasts and inhibited expression of insulin-stimulated p-AKTSer473 in myotubes. The accumulations of autophagosome assessed by tandem fluorescent-tagged LC3 demonstrated that autophagic flux was impaired in both palmitate-treated myoblasts and myotubes. Resveratrol protected muscle cells from palmitate-induced cellular senescence, apoptosis during differentiation, and insulin resistance via ameliorating autophagic flux. The direct influence of autophagic flux on development of cellular senescence and insulin resistance was confirmed by blockage of autophagic flux with chloroquine. In conclusion, impairment of autophagic flux is crucial for palmitate-induced cellular senescence and insulin resistance in muscle cells. Restoring autophagic flux by resveratrol could be a promising approach to prevent cellular senescence and ameliorate insulin resistance in muscle.

KEYWORDS:

Autophagic flux; Cellular senescence; Insulin resistance; Resveratrol

PMID:
29976399
DOI:
10.1016/j.jfda.2018.01.006
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