SIRT1 mRNA expression may be associated with energy expenditure and insulin sensitivity
Open accessAbstract
OBJECTIVE: Sirtuin 1 (SIRT1) is implicated in the regulation of mitochondrial function, energy metabolism, and insulin sensitivity in rodents. No studies are available in humans to demonstrate that SIRT1 expression in insulin-sensitive tissues is associated with energy expenditure and insulin sensitivity. RESEARCH DESIGN AND METHODS: Energy expenditure (EE), insulin sensitivity, and SIRT1 mRNA adipose tissue expression (n = 81) were measured by indirect calorimetry, hyperinsulinemic-euglycemic clamp, and quantitative RT-PCR in 247 nondiabetic offspring of type 2 diabetic patients. RESULTS: High EE during the clamp (r = 0.375, P = 2.8 x 10(-9)) and high DeltaEE (EE during the clamp - EE in the fasting state) (r = 0.602, P = 2.5 x 10(-24)) were associated with high insulin sensitivity. Adipose tissue SIRT1 mRNA expression was significantly associated with EE (r = 0.289, P = 0.010) and with insulin sensitivity (r = 0.334, P = 0.002) during hyperinsulinemic-euglycemic clamp. Furthermore, SIRT1 mRNA expression correlated significantly with the expression of several genes regulating mitochondrial function and energy metabolism (e.g., peroxisome proliferator-activated receptor gamma coactivator-1beta, estrogen-related receptor alpha, nuclear respiratory factor-1, and mitochondrial transcription factor A), and with several genes of the respiratory chain (e.g., including NADH dehydrogenase [ubiquinone] 1alpha subcomplex 2, cytochrome c, cytochrome c oxidase subunit IV, and ATP synthase). CONCLUSIONS: Impaired stimulation of EE by insulin and low SIRT1 expression in insulin-sensitive tissues is likely to reflect impaired regulation of mitochondrial function associated with insulin resistance in humans.
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SIRT1 protects against ageing-associated metabolic diseases such as glucose intolerance and cancer.
“As such, SIRT1 confers protection against ageing-associated metabolic diseases such as glucose intolerance and cancer (Herranz et al., 2010; Pearson et al., 2008; Rutanen et al., 2010).”
From Calorie Restriction-like Effects of 30 Days of Resveratrol Supplementation on Energy Metabolism and Metabolic Profile in Obese Humans (2011) · cites this paper as Rutanen et al., 2010
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- Authors
- Rutanen, J., Yaluri, N., Modi, S., Pihlajamäki, J., Vänttinen, M., Itkonen, P., Kainulainen, S., Yamamoto, H., Lagouge, M., Sinclair, D. A., Elliott, P., Westphal, C., Auwerx, J., & Laakso, M.
- Affiliations
- Kuopio University Hospital (FI)
- Department of Clinical Radiology, University of Kuopio, Kuopio, Finland;
- Centre National de la Recherche Scientifique (FR)
- Harvard University (US)
- Sirtris Pharmaceuticals, Cambridge, Massachusetts.
- Corresponding author
- Laakso, Markku
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2010-01-27
- Volume
- 59
- Issue
- 4
- Pages
- 829-835
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC2844830
- OpenAlex
- W2118953826
- Cited by
- 104
- References
- 34
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 2 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 5 · 2019: 5 · 2018: 7 · 2017: 5 · 2016: 8 · 2015: 12 · 2014: 3 · 2013: 7 · 2012: 18
- FWCI
- 5.74
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Funders
- GlaxoSmithKline
- Academy of Finland
- Centre National de la Recherche Scientifique
- National Institutes of Health
- National Institute on Aging (P01AG027916, R01AG028730, R01AG019719)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK069966, R01DK069966)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- SIRT1, energy expenditure, insulin sensitivity, adipose tissue, mitochondrial function, energy metabolism, insulin resistance, type 2 diabetes, PGC-1β, NRF1, TFAM
- MeSH terms
- Adult, Animals, Crosses, Genetic, Diabetes Mellitus, Type 2, Energy Metabolism, Female, Gene Expression Regulation, Humans, Male, Mice, Inbred BALB C, Mice, Inbred DBA, Reference Values, RNA, Messenger, Body Mass Index, Glucose Intolerance, Muscle, Skeletal, Mice, Sirtuin 1
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