Resveratrol improves high-fat diet induced insulin resistance by rebalancing subsarcolemmal mitochondrial oxidation and antioxidantion
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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SS mitochondria are the main energy provider related to substrate oxidation and insulin action, while IMF mitochondria play a more direct role in supporting muscle contractions.
“This is not surprising because SS mitochondria are the main energy provider related to substrate oxidation and insulin action, while IMF mitochondria play a more direct role in supporting muscle contractions [88].”
From Mitochondrial Adaptation in Skeletal Muscle: Impact of Obesity, Caloric Restriction, and Dietary Compounds (2024) · cites this paper as [88]
Resveratrol countered high-fat diet-induced metabolic deterioration via mechanisms partly relying on its beneficial effects on mitochondrial health and function.
“resveratrol countered high-fat diet-induced metabolic deterioration with a mechanisms which relayed albeit in part, on its beneficial effects on mitochondrial health and function (Haohao et al., 2015).”
From Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet (2019) · cites this paper as Haohao et al., 2015
In rats, a high-fat diet induced insulin resistance, downregulated SIRT1 and SIRT3, inhibited mitochondrial biogenesis, and decreased mtDNA.
“While a high-fat diet induced insulin resistance, downregulated SIRT1 and SIRT3, inhibited mitochondria biogenesis and decreased mtDNA”
From Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet (2019) · cites this paper as Haohao et al., 2015
In rats, resveratrol counteracts the deleterious effect of a high-fat diet on metabolic and mitochondrial health.
“Furthermore, resveratrol has been shown to counteract the deleterious effect of a high-fat diet on metabolic and mitochondria health in rats.”
From Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet (2019) · cites this paper as Haohao et al., 2015
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- Authors
- Haohao, Z., Guijun, Q., Juan, Z., Wen, K., & Lulu, C.
- Affiliations
- First Affiliated Hospital of Zhengzhou University (CN)
- Wuhan Union Hospital (CN)
- Corresponding author
- Lulu, Chen
- Venue
- Journal of Physiology and Biochemistry
- Published
- 2015-02-17
- Volume
- 71
- Issue
- 1
- Pages
- 121-131
- ISSN
- 1138-7548 (ISSN-L)
- 1877-8755
- OpenAlex
- W1982445419
- Cited by
- 42
- References
- 29
- Citations by year
- 2025: 4 · 2024: 1 · 2023: 5 · 2022: 2 · 2021: 3 · 2020: 4 · 2019: 6 · 2018: 5 · 2017: 6 · 2016: 3 · 2015: 3
- FWCI
- 2.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Physiology and Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81300656)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- resveratrol, insulin resistance, high-fat diet, skeletal muscle, subsarcolemmal mitochondria, interfibrillar mitochondria, mitochondrial oxidative stress, antioxidant enzymes, SIRT1, SIRT3, mitochondrial biogenesis, mitochondrial DNA, reactive oxygen species, malondialdehyde
- MeSH terms
- Resveratrol, Animals, Antioxidants, DNA, Mitochondrial, Insulin, Insulin Resistance, Male, Mitochondria, Oxidation-Reduction, Stilbenes, Rats, Sprague-Dawley, Muscle, Skeletal, Rats, Sirtuin 1, Sirtuin 3, Diet, High-Fat
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