SIRT1 mRNA Expression May Be Associated With Energy Expenditure and Insulin Sensitivity

  1. Markku Laakso1
  1. 1Department of Medicine, University of Kuopio and Kuopio University Hospital, Kuopio, Finland;
  2. 2Department of Clinical Radiology, University of Kuopio, Kuopio, Finland;
  3. 3Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique/Institut National de la Santé et de la Recherche Médicale/Université Louis Pasteur, Illkirch, France;
  4. 4Laboratory of Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland;
  5. 5Department of Pathology and Glenn Labs for Aging Research, Harvard Medical School, Boston, Massachusetts;
  6. 6Sirtris Pharmaceuticals, Cambridge, Massachusetts.
  1. Corresponding author: Markku Laakso, markku.laakso{at}


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 × 10−9) and high ΔEE (EE during the clamp − EE in the fasting state) (r = 0.602, P = 2.5 × 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 γ coactivator-1β, estrogen-related receptor α, nuclear respiratory factor-1, and mitochondrial transcription factor A), and with several genes of the respiratory chain (e.g., including NADH dehydrogenase [ubiquinone] 1α 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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    • Received August 11, 2009.
    • Accepted January 20, 2010.

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