Role of autophagy in adipose tissue and in peripheral nervous system in diabetes type 2, obesity and metabolic syndrome

Background: Pathophysiology of obesity is closely associated with enhanced autophagy in adipose tissue (AT) and in peripheral nerves (PN). Autophagic process can promote survival or activate cell death. Therefore, we examined the occurrence of autophagy in AT of type 2 diabetes (T2D) patients in comparison to obese and lean individuals without diabetes. Moreover, we analysed the autophagy in AT and in peripheral nerves of WOKW rats with metabolic syndrome (MS) compared to LEW.1W control rats.

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, upregulated expression of LC3 and Atg5 mRNA, along with decreased p62 and mTOR protein levels. Increased autophagy occurred together with AT inflammation.

WOKW rats with MS showed significant up-regulated autophagy and macrophage infiltration in the sciatic nerves and AT without signs of neuropathy or diabetes.

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.

Furthermore, we propose that up-regulated autophagy and inflammatory cells may exert a protective role against diabetes and peripheral neurodegeneration in WOKW rat model.