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}kuh.fi.

Abstract

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.

Footnotes

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Received August 11, 2009.
    • Accepted January 20, 2010.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

| Table of Contents

This Article

  1. Diabetes vol. 59 no. 4 829-835
  1. Online-Only Appendix
  2. All Versions of this Article:
    1. db09-1191v1
    2. 59/4/829 most recent