Adipose tissue function and dysfunction: organ cross talk and metabolic risk

Abstract

OBESITY IS A COMPLEX AND ESCALATING metabolic disorder characterized by a positive disequilibrium between energy intake and energy expenditure. The consequent expansion of the adipose organ, and in particular of visceral fat depots, increases the risk of developing obesity complications such as insulin resistance, type 2 diabetes, atherosclerosis, obstructive sleep apnea, steatohepatitis, and cardio- and cerebrovascular diseases. In this context, several clinical and biochemical elements may act as risk factors for cardiovascular disease, including low high-density lipoprotein cholesterol, high triglycerides, increased concentrations of apolipoprotein B, and small, dense low-density lipoprotein particles, arterial hypertension, hyperglycemia, hyperuricemia, and microalbuminuria. The more risk factors are present in any individual, the higher the risk of transition to diabetes and/or cardiovascular disease (10). The increase in abdominal circumference is the clinical parameter that probably best identifies the risk of clustering other features of the insulin resistance/metabolic syndrome (2) and of predicting overall mortality (8). Recent experimental evidence suggests that adipocytes located in the abdominal region display distinct cellular features compared with adipocytes from other fat depots (5). Consequently, a specific dysfunction of the visceral adipocyte has been proposed as the pathophysiological basis for the negative consequences of abdominal obesity. Although the epidemiological association between fat accumulation and excess risk of diabetes and of cardiovascular disease is striking, the biological mechanisms underlying the adverse impact of adipose tissue remain incompletely defined. Evidently, adipose tissue is not only responsible for storage of energy, but operates as a highly active and dynamic tissue. Adipocytes produce hormones and cytokines, collectively called adipokines, with pleiotropic effects on multiple tissues, leading to fine tuning of fuel utilization, energy homeostasis, and cardiovascular function. It should also be recognized that the functional attitude of visceral and subcutaneous adipocytes is programmed quite early during development and differentiation, due to inherent characteristics of the adipocyte precursors, multipotent cells that are resident in each fat depot and possess defined depot-specific genetic, biochemical, and metabolic features (3, 7, 9, 12, 15). Thus, the biological specificity of the distinct adipose tissue depots may reside in the different biological profile of the resident cells, including the adipocyte precursors.