Autophagy in adipose tissue of patients with obesity and type 2 diabetes

Mol Cell Endocrinol. 2015 Jul 5:409:21-32. doi: 10.1016/j.mce.2015.03.015. Epub 2015 Mar 26.

Abstract

Background: Pathophysiology of obesity is closely associated with enhanced autophagy in adipose tissue (AT). Autophagic process can promote survival or activate cell death. Therefore, we examine the occurrence of autophagy in AT of type 2 diabetes (T2D) patients in comparison to obese and lean individuals without diabetes.

Methodology/principal findings: Numerous autophagosomes accumulated within adipocytes were visualized by electron transmission microscopy and by immunofluorescence staining for autophagy marker LC3 in obese and T2D patients. Increased autophagy was demonstrated by higher LC3-II/LC3-I ratio, up-regulated expression of LC3 and Atg5 mRNA, along with decreased p62 and mTOR protein levels. Increased autophagy occurred together with AT inflammation.

Conclusions: Our data suggest fat depot-related differences in autophagy regulation. In subcutaneous AT, increased autophagy is accompanied by increased markers of apoptosis in patients with obesity independently of T2D. In contrast, in visceral AT only in T2D patients increased autophagy was related to higher markers of apoptosis.

Keywords: Adipose tissue; Autophagy; Inflammation; Obesity; T2D.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism*
  • Adipose Tissue / ultrastructure
  • Apoptosis
  • Autophagy*
  • Autophagy-Related Protein 5
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Gene Expression Regulation
  • Humans
  • Intra-Abdominal Fat / metabolism
  • Intra-Abdominal Fat / pathology*
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Obesity / genetics
  • Obesity / metabolism
  • Obesity / physiopathology*
  • Subcutaneous Fat / metabolism
  • Subcutaneous Fat / pathology*
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • ATG5 protein, human
  • Autophagy-Related Protein 5
  • MAP1LC3A protein, human
  • MAP1LC3B protein, human
  • Microtubule-Associated Proteins
  • MTOR protein, human
  • TOR Serine-Threonine Kinases