Chapter 6 - Cross-Talk between Autophagy and Apoptosis in Adipose Tissue: Role of Ghrelin

Abstract

Excess adiposity contributes to alterations in the molecular mechanisms and cell-intrinsic pathways in the adipose tissue that predispose to the development of obesity-associated metabolic disturbances, such as insulin resistance, type 2 diabetes or the metabolic syndrome. The pathological expansion of the adipose tissue in the onset of obesity contributes to the formation of hypoxic areas, leading to adipocyte apoptosis. Recently, another type of programmed cell death, namely autophagy, has been shown to be activated in fat depots of obese subjects. Autophagy constitutes a major cellular degradation process involving intracellular trafficking towards the lysosome. The underlying mechanisms whereby apoptosis and autophagy are regulated in the adipose tissue are not fully understood and the literature is still scarce. We have recently reported that insulin resistance is associated with an aggravation in human adipocytes of the apoptosis and expression of autophagy-related genes BECN1, ATG5 and ATG7, involved in the initiation and elongation of autophagosomes. Our data showed that ghrelin, a gut-derived hormone involved in the regulation of energy balance, operates as a negative regulator of tumor necrosis factor α (TNF-α)-induced apoptosis and autophagy in visceral adipocytes. The imbalance between ghrelin and TNF-α in states of insulin resistance may contribute to the altered apoptosis and autophagy found in adipose tissue of patients with type 2 diabetes. A better understanding of the pathways involved in programmed cell death in adipose tissue is needed for fully disentangling the etiopathology of obesity-associated type 2 diabetes.