Background: Sirtuins are NAD+-dependant protein deacetylases that target histones, transcription factors, co-regulators, as well as metabolic enzymes to adapt gene expression and metabolic activity in response to the cellular energy state. SIRT1 and SIRT2 are two important enzymes of sirtuin family. SIRT1 has an important role in glucose metabolism and improves glucose homeostasis. It can also regulate fatty acid oxidation and hepatic cholesterol and bile acid metabolism. SIRT2 has an antioxidant activity and negatively regulates insulin resistance.
Objective and hypotheses: The aim of this study was to evaluate SIRT1 and SIRT2 gene expression in peripheral blood mononuclear cells (PBMCs) of children and adolescents with obesity and their association with metabolic parameters and insulin resistance.
Method: children and adolescents (30 obese and 30 age and gender matched control subjects), (815 year old), were selected. PBMCs were separated and their total RNA was extracted. After cDNA synthesis, SIRT1 and SIRT2 gene expression were analysed by real-time PCR. Relative differences in gene expression were calculated by ΔCt method using β-actin as a normalizer. Serum insulin was measured using ELISA, and insulin resistance (IR) was calculated by the Homeostasis Model of Assessment of Insulin Resistance (HOMA-IR). Fasting plasma glucose, triglyceride, total cholesterol, LDL-C and HDL-C were also measured.
Results: Expression of SIRT1 gene was significantly diminished in obese subjects compared to control ones (0.33±0.02 vs 1.37±0.25) (P=0.000). It was also significantly lower in obese children with IR compared to obese children without IR (0.33±0.079 vs 0.97±0.17) (P=0.008). There was a trend toward a lower SIRT2 expression in obese subjects but the difference was not significant (1.88±0.19 vs 2.83±0.36) (P=0.057). SIRT1 expression was significantly correlated with BMI and waist circumference as well as insulin and MOMA-IR. SIRT2 was significantly correlated with SIRT1 and HDL-C.
Conclusion: SIRT1 is decreased in obesity and is associated with insulin resistance in children and adolescents. Targeting SIRT1 can be valuable in treating obesity and insulin resistance in childhood and adolescence.
Funding: This work was supported by Endocrinology and metabolism Research Institute, Tehran University of Medical Sciences (grant number 1392-02-104-1707).
01 - 03 Oct 2015
European Society for Paediatric Endocrinology