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Resveratrol improves high-fat diet induced insulin resistance by rebalancing subsarcolemmal mitochondrial oxidation and antioxidantion

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Abstract

Although resveratrol (RES) is thought to be a key regulator of insulin sensitivity in rodents, the exact mechanism underlying this effect remains unclear. Therefore, we sought to investigate how RES affects skeletal muscle oxidative and antioxidant levels of subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondrial populations in high-fat diet (HFD)-induced insulin resistance (IR) rats. Systemic and skeletal muscle insulin sensitivity together with expressions of several genes related to mitochondrial biogenesis and skeletal muscle SIRT1, SIRT3 protein levels were studied in rats fed a normal diet, a HFD, and a HFD with intervention of RES for 8 weeks. Oxidative stress levels and antioxidant enzyme activities were assessed in SS and IMF mitochondria. HFD fed rats exhibited obvious systemic and skeletal muscle IR as well as decreased SIRT1 and SIRT3 expressions, mitochondrial DNA (mtDNA), and mitochondrial biogenesis (p < 0.05). Both SS and IMF mitochondria demonstrated elevated reactive oxygen species (ROS) and malondialdehyde (MDA) levels. In addition, SS mitochondrial antioxidant enzyme activities were significantly lower, while IMF mitochondrial antioxidant enzyme activities were higher (p < 0.05). By contrast, RES treatment protected rats against diet induced IR, increased SIRT1 and SIRT3 expressions, mtDNA, and mitochondrial biogenesis (p < 0.05). Moreover, the activities of SS and IMF mitochondrial antioxidant enzymes were increased, which reverted the increased SS mitochondrial oxidative stress levels (p < 0.05). This study suggests that RES ameliorates insulin sensitivity consistent with improved SIRT3 expressions and rebalance between SS mitochondrial oxidative stress and antioxidant competence in HFD rats.

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Abbreviations

RES:

Resveratrol

SS:

Subsarcolemmal

IMF:

Intermyofibrillar

HFD:

High-fat diet

IR:

Insulin resistance

mtDNA:

Mitochondrial DNA

ROS:

Reactive oxygen species

MDA:

Malondialdehyde

TA:

Tibialis anterior

PGC-1α:

Peroxisome proliferator-activated receptor-γ coactivator-1α

NRF-1:

Nuclear respiratory factor-1

mtTFA:

Mitochondrial transcription factor A

tSOD:

Total superoxide dismutase

CAT:

Catalase

GPx:

Glutathione peroxidase

FBG:

Fasting blood glucose

Fins:

Fasting insulin

GIR:

Glucose infusion rate

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Acknowledgments

This work was supported by National Natural Science Foundation of China grant 81300656.

Conflict of interest

The authors declare that they have no conflict of interest regarding this manuscript.

Author contributions

All authors participated in the design, interpretation of the studies and analysis of the data, and review of the manuscript; H-HZ, JZ, XH, and WK conducted the experiments; L-LC, H-HZ, and QG wrote the manuscript.

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Authors and Affiliations

  1. Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, 40 Daxue Road, Zhengzhou, 450052, People’s Republic of China

    Zhang Haohao & Qin Guijun

  2. Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science Technology, Wuhan, 430022, China

    Zheng Juan, Kong Wen & Chen Lulu

Authors
  1. Zhang Haohao
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  2. Qin Guijun
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  3. Zheng Juan
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  4. Kong Wen
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  5. Chen Lulu
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Corresponding author

Correspondence to Chen Lulu.

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Haohao, Z., Guijun, Q., Juan, Z. et al. Resveratrol improves high-fat diet induced insulin resistance by rebalancing subsarcolemmal mitochondrial oxidation and antioxidantion. J Physiol Biochem 71, 121–131 (2015). https://doi.org/10.1007/s13105-015-0392-1

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  • DOI: https://doi.org/10.1007/s13105-015-0392-1

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