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

J Kosacka; M Kern; N Klöting; S Paeschke; A Rudich; Y Haim; M Gericke; H Serke; M Stumvoll; I Bechmann; M Nowicki; M Blüher

doi:10.1016/j.mce.2015.03.015

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.

Authors

J Kosacka¹, M Kern², N Klöting³, S Paeschke², A Rudich⁴, Y Haim⁴, M Gericke⁵, H Serke⁵, M Stumvoll², I Bechmann⁵, M Nowicki⁵, M Blüher²

Affiliations

¹ Department of Medicine, University of Leipzig, Liebigstraße 21, D-04103 Leipzig, Germany. Electronic address: Joanna.Kosacka@medizin.uni-leipzig.de.
² Department of Medicine, University of Leipzig, Liebigstraße 21, D-04103 Leipzig, Germany.
³ Department of Medicine, University of Leipzig, Liebigstraße 21, D-04103 Leipzig, Germany; Integrated Research and Treatment Center (IFB) Adiposity Diseases, Liebigstraße 21, D-04103 Leipzig, Germany.
⁴ Department of Clinical Biochemistry and Pharmacology, National Institute of Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva 84103, Israel.
⁵ Institute of Anatomy, University of Leipzig, Liebigstraße 13, D-04103 Leipzig, Germany.

PMID: 25818883
DOI: 10.1016/j.mce.2015.03.015

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