SIRT1 mRNA expression may be associated with energy expenditure and insulin sensitivity

Diabetes. 2010 Apr;59(4):829-35. doi: 10.2337/db09-1191. Epub 2010 Jan 27.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Body Mass Index
  • Crosses, Genetic
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Energy Metabolism / genetics
  • Female
  • Gene Expression Regulation
  • Glucose Intolerance / genetics
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred DBA
  • Muscle, Skeletal / physiology
  • Muscle, Skeletal / physiopathology
  • RNA, Messenger / genetics*
  • Reference Values
  • Sirtuin 1 / genetics*


  • RNA, Messenger
  • SIRT1 protein, human
  • Sirt1 protein, mouse
  • Sirtuin 1