Endocrine Abstracts

Introduction and aims: Autophagy is an essential process for cell homeostasis that implies recycling and degradation of damaged organelles and long-lived proteins. It is induced during caloric restriction (in order to obtain energy) or other stress-inducing conditions. Autophagy is initiated by autophagosome formation, a double-membrane vesicle which engulfs cellular components and delivers them for degradation by fusing with lysosomes. Thus, proper autophagy regulation favours cell survival thanks to the turn-over of damaged organelles and energy supply. Although obesity is frequently associated with other metabolic diseases, there are also non-diabetic obese subjects as well as diabetic or insulin-resistant non-obese individuals. For this reason, it has been suggested that functional state of adipose tissue (AT) rather than AT size is which determines the development of metabolic disorders. Despite the fact that previous associations have been described between AT autophagy activation and obesity and diabetes, these paradoxical phenotypes have not been studied, and it has only been analyzed a few of the molecules implied in AT autophagy regarding obesity and carbohydrate disorders in human studies.Thus, the aim of this study was to analyze AT gene expression of molecules implied in the different steps of autophagy according to the degree of obesity and the glycemic status.

Methods: The expression of genes implied in the different steps of autophagy in visceral and subcutaneous AT (VAT and SAT, respectively) was analyzed in the study subjects classified according to their BMI in lean, oeverweight, obese and morbidly obese subjects and to their glycemic status (defined by glucose levels and the insulin resistance index HOMA-IR) in diabetic/high-insulin-resistant subjects (D/HIR) and low-insulin-resistant subjects (LIR).

Results: Comparisons between D/HIR and LIR subjects paired by BMI showed a diminished VAT and SAT expression of genes related to autophagosome formation in patients with alterations in glucose metabolism which was more noticeable in morbidly obese subjects. Significant differences regarding BMI were only found in LIR subjects, having LIR lean subjects higher VAT and SAT expression of these genes than LIR subjects with higher BMI. Gene expression of molecules implied in autophagosome induction and elongation correlated significantly and negatively with HOMA-IR and BMI.

Conclusion: Low autophagy induction in AT is related to a higher susceptibility to insulin resistance and diabetes development which is more noticeable in extreme obesity.