Resveratrol improves ex vivo mitochondrial function but does not affect insulin sensitivity or brown adipose tissue in first degree relatives of patients with type 2 diabetes
Open accessAbstract
Objective Resveratrol supplementation improves metabolic health in healthy obese men, but not in patients with type 2 diabetes (T2D) when given as add-on therapy. Therefore, we examined whether resveratrol can enhance metabolic health in men at risk of developing T2D. Additionally, we examined if resveratrol can stimulate brown adipose tissue (BAT). Methods Thirteen male first degree relatives (FDR) of patients with T2D received resveratrol (150 mg/day) and placebo for 30 days in a randomized, placebo controlled, cross-over trial. Results Resveratrol significantly improved ex vivo muscle mitochondrial function on a fatty acid-derived substrate. However, resveratrol did not improve insulin sensitivity, expressed as the rate of glucose disposal during a two-step hyperinsulinemic-euglycemic clamp. Also, intrahepatic and intramyocellular lipid content, substrate utilization, energy metabolism, and cold-stimulated 18 F-FDG glucose uptake in BAT (n = 8) remained unaffected by resveratrol. In vitro experiments in adipocytes derived from human BAT confirmed the lack of effect on BAT. Conclusions Resveratrol stimulates muscle mitochondrial function in FDR males, which is in concordance with previous results. However, no other metabolic benefits of resveratrol were found in this group. This could be attributed to subject characteristics causing alterations in metabolism of resveratrol and thereby affecting resveratrol's effectiveness. ClinicalTrials.gov ID NCT02129595 .
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Resveratrol did not induce an increase in insulin sensitivity in first-degree relatives of type 2 diabetic individuals.
“resveratrol did not induce an increase in insulin sensitivity in these individuals”
From Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet (2019) · cites this paper as de Ligt et al., 2018
In first-degree relatives of type 2 diabetic individuals, resveratrol increases mitochondrial respiration on octanoyl-carnitine.
“Remarkably, the effect of resveratrol was confirmed in the first-degree relatives of type 2 diabetic individuals with resveratrol increasing mitochondrial respiration on octanoyl-carnitine (de Ligt et al., 2018).”
From Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet (2019) · cites this paper as de Ligt et al., 2018
A small increase in mitochondrial function may not be sufficient to enhance insulin sensitivity if not supported by higher levels of physical activity.
“suggesting that a small increase in mitochondrial function may not be sufficient to enhance insulin sensitivity if not supported by higher levels of physical activity (de Ligt et al., 2018).”
From Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet (2019) · cites this paper as de Ligt et al., 2018
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“Remarkably, the effect of resveratrol was confirmed in the first-degree relatives of type 2 diabetic individuals with resveratrol increasing mitochondrial respiration on octanoyl-carnitine (de Ligt et al., 2018).”
BackgroundRemie, C. M., Roumans, K. H., Moonen, M. P., Connell, N. J., Havekes, B., Mevenkamp, J., Lindeboom, L., de Wit, V. H., van de Weijer, T., Aarts, S. A., et al. (2020) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqaa072 · Cited by 160 · see citing works
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Self-citation
- Authors
- de Ligt, M., Bruls, Y. M. H., Hansen, J., Habets, M.-F., Havekes, B., Nascimento, E. B. M., Moonen-Kornips, E., Schaart, G., Schrauwen-Hinderling, V. B., van Marken Lichtenbelt, W., & Schrauwen, P.
- Affiliations
- Maastricht University Medical Centre (NL)
- Corresponding author
- Schrauwen, Patrick
- Venue
- Molecular Metabolism
- Publisher
- Elsevier BV
- Published
- 2018-06
- Volume
- 12
- Pages
- 39-47
- ISSN
- 2212-8778 (ISSN-L)
- PMC
- PMC6001939
- OpenAlex
- W2801147755
- Cited by
- 79
- References
- 43
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 4 · 2023: 12 · 2022: 11 · 2021: 21 · 2020: 13 · 2019: 7 · 2018: 2
- FWCI
- 5.95
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecular Metabolism (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Funders
- Diabetes Fonds (2012.00.1525)
- Netherlands Cardiovascular Research Initiative: an initiative with support of the Dutch Heart Foundation (CVON2014-02 ENERGISE)
- Dutch Heart Foundation
- 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, type 2 diabetes, first-degree relatives, insulin sensitivity, brown adipose tissue, fatty acid oxidation, hepatic fat content, intramyocellular lipid, hyperinsulinemic-euglycemic clamp, adipocytes, metabolic health
- MeSH terms
- Resveratrol, Aged, Adipose Tissue, Brown, Diabetes Mellitus, Type 2, Fatty Acids, Glucose, Humans, Hypoglycemic Agents, Insulin Resistance, Male, Middle Aged, Mitochondria, Muscle, Pedigree
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