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

Int J Mol Sci. 2019 Mar 6;20(5):1153. 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.

Keywords: NF-κB; PPAR-γ; SREBP-1; obesity; pre-diabetes; sirtuin 6.

MeSH terms

  • Abdominal Fat / metabolism*
  • Adult
  • Down-Regulation / drug effects
  • Female
  • Humans
  • Male
  • Metformin / administration & dosage*
  • Metformin / pharmacology
  • Middle Aged
  • NF-kappa B / metabolism
  • Overweight / drug therapy
  • Overweight / metabolism*
  • PPAR gamma / metabolism
  • Prediabetic State / drug therapy
  • Prediabetic State / metabolism*
  • Prospective Studies
  • Sirtuins / metabolism*
  • Sterol Regulatory Element Binding Protein 1 / metabolism

Substances

  • NF-kappa B
  • PPAR gamma
  • PPARG protein, human
  • SREBF1 protein, human
  • Sterol Regulatory Element Binding Protein 1
  • Metformin
  • SIRT6 protein, human
  • Sirtuins