Abdominal Fat SIRT6 Expression and Its Relationship with Inflammatory and Metabolic Pathways in Pre-Diabetic Overweight Patients.

Nunzia D’Onofrio,Raffaele Marfella,Celestino Sardu,Gorizio Pieretti,Maria Rosaria Rizzo,Gianfranco Nicoletti,Nicola Passariello,Maria Luisa Balestrieri,Antonio Gambardella,Feliciano Ciccarelli,Michelangela Barbieri

doi:10.3390/ijms20051153

Abstract

The role of sirtuin 6 (SIRT6) in adipose abdominal tissue of pre-diabetic (pre-DM) patients is poorly known. Here, we evaluated SIRT6 expression in visceral abdominal fat of obese pre-diabetic patients and the potential effects of metformin therapy. Results indicated that obese pre-DM subjects showed low SIRT6 protein expression and high expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), peroxisome proliferator-activated receptor gamma (PPAR-γ), and sterol regulatory element-binding transcription factor 1 (SREBP-1). Obese pre-DM patients showed high values of glucose, insulin resistance (HOMA-IR), C reactive protein (CRP), nitrotyrosine, tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6), and low values of insulin (p < 0.05). Of note, abdominal fat tissue of obese pre-DM patients treated with metformin therapy presented higher SIRT6 expression and lower NF-κB, PPAR-γ, and SREBP-1 expression levels compared to pre-DM control group. Collectively, results show that SIRT6 is involved in the inflammatory pathway of subcutaneous abdominal fat of obese pre-DM patients and its expression responds to metformin therapy.

Highlights

Visceral fat and superficial adipose tissue of obese patients express cytokines cross-talking with the cardiovascular system [1]
sirtuin 6 (SIRT6) regulates the activities of several non-histone proteins by lysine deacetylation, modulating the expression of target genes involved in the control of glucose homeostasis, energy metabolism, aging, oxidative stress, insulin resistance, lipids metabolism, and inflammation [5,6,7]
Results indicated that obese pre-DM patients showed higher values of inflammatory and oxidative stress markers, and lower values of SIRT6 tissue protein expression than normoglycemic subjects, with a beneficial effect exerted by metformin therapy

Summary

Introduction

Visceral fat and superficial adipose tissue of obese patients express cytokines cross-talking with the cardiovascular system [1]. Less is known about the specific molecular effectors regulated by SIRT6 in adipose tissue of obese pre-DM patients and the possible effect of metformin therapy. In this context, we aimed at investigating the possible role of SIRT6 in the abdominal fat of overweight pre-DM patients. We aimed at investigating the possible role of SIRT6 in the abdominal fat of overweight pre-DM patients To this end, protein expression levels of SIRT6 and its molecular targets were evaluated in adipose tissue samples from normoglycemic (NG), obese pre-DM, and obese pre-DM subjects under metformin therapy. The possible correlation between plasma biomarkers of inflammation, glucose homeostasis, and lipid metabolism and the tissue expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) [10], PPAR-γ [11], and sterol regulatory element-binding transcription factor 1 (SREBP-1) [12] was investigated

Methods

Results

Conclusion