ACYLATION STIMULATING PROTEIN/C3ADESARG, IN SPECIFIC POPULATIONS AND METABOLIC STATES: ROLE OF ADIPOCYTE ADIPOKINE DYSFUNCTION IN OBESITY AND ITS CONSEQUENCES

Background and Aim: Obesity is associated with many major metabolic disorders, especially diabetes, cardiovascular disorders, and fatty liver disease. Aimed at developing effective therapies for obesity and its complications, new research has intensified to elucidate the pathophysiological mechanisms by which obesity induces or amplifies its major adverse consequences. Adipose tissue, as an endocrine organ, secretes several hormones termed adipokines that are involved in energy homeostasis and weight regulation. Methods: Dysfunction of adipokine pathways has been recognized as a key etiological factor of obesity-induced disorders. Acylation stimulating protein (ASP) is an adipokine that stimulates triglyceride synthesis and storage in adipose tissue by enhancing glucose and fatty acid uptake. ASP acts via its receptor C5L2. These studies investigate several human populations under varying external and internal conditions and evaluates changes in adipokines, in particular ASP and its related proteins, in association with obesity determinants. This overall aim is achieved through four studies including the following: I) evaluation of adipokines in healthy overweight/obese adults consuming glucose- or fructose-sweetened beverages to determine the effects of diet composition on adipose tissue function II) a cross-sectional populationbased study to determine fasting serum ASP and its relationships with cardiometabolic risk factors in a relatively high risk adult population III) a study on severely-obese pre/postmenopausal women, who underwent bariatric surgery, to determine associations of hepatic gene expression of complement C3 related receptors, sex hormones, adipokines and metabolic profiles as well as evaluating obesity improvement after surgery IV) a study on women with a wide age and BMI range to determine plasma adipokine levels and adipose tissue depot gene expression of C3 and related receptors in association with metabolic syndrome criteria, ovarian hormones and metabolic profile. Conclusion: We found different responses of ASP and its receptor according to gender, metabolic disorder, sex hormone levels, organ involvement and diet composition: all factors critical as obesity determinants. The results presented here demonstrate that ASP may mediate the link between obesity-related exogenous factors and biologic events that lead to obesity consequences. In conclusion, these findings validate that obesity is a low-grade inflammatory status with multi-organ involvement, evidencing sex differences and dynamic interactions between immune and metabolic response determinants.

کلیدواژه ها:

acylation stimulating protein ، obesity ، adipkines ، adipose tissue dysfunction