Reduced gene expression of sirtuins and active AMPK levels in children and adolescents with obesity and insulin resistance

Abstract

Sirtuins, including SIRT1 and SIRT2, are longevity-associated deacetylase enzymes that modulate metabolic homeostasis in response to the cellular energy state. Adenosine monophosphate activated protein kinase (AMPK) and SIRT1 are interrelated and share several common target pathways. This study aimed to evaluate the SIRT1 and SIRT2 gene expression in peripheral blood mononuclear cells (PBMCs) as well as plasma levels of AMPK, in obese children and adolescents. Participants included 60 children and adolescents (30 obese and 30 age- and gender-matched control subjects). Real-time polymerase chain reaction (PCR) was used to assess the SIRT1 and SIRT2 gene expression in PBMCs. Serum phospho-AMPK and insulin were measured using enzyme-linked immunosorbent assay (ELISA), and insulin resistance (IR) was calculated by the Homeostasis Model of Assessment of Insulin Resistance (HOMA-IR). Glucose and lipid profile were also measured. SIRT1 gene expression and phospho-AMPK plasma levels were significantly diminished in obese subjects compared to the control group, and both SIRT1 and SIRT2 were significantly lower in obese children with IR compared to those without IR. SIRT1 expression revealed significant negative correlations with body mass index and waist circumference as well as insulin and HOMA-IR and a positive correlation with AMPK. SIRT2 negatively correlated with SIRT1 and positively correlated with high density lipoprotein-cholesterol (HDL-C). SIRT1 and SIRT2 expression and AMPK levels decrease in children with obesity and IR. Targeting SIRT1 can be valuable in preventing obesity-associated IR in childhood and adolescence.