Regional Adiposity and Insulin Resistance

It is well recognized that persons with generalized obesity suffer from a high risk of insulin resistance and its metabolic complications, such as type 2 diabetes mellitus, hypertriglyceridemia, low levels of high density lipoprotein cholesterol, hypertension, hepatic steatosis, hyperuricemia, and atherosclerotic vascular disease (1–3). However, whether accumulation of adipose tissue in a particular anatomical compartment (regional adiposity) confers an excess risk of insulin resistance and its complications remains controversial. This controversy at the clinical and molecular level has been discussed in several recent review articles (4 –9). This article focuses on the clinical evidence related to impact of regional adiposity on insulin resistance. From an anatomical standpoint, the most peculiar regional adipose tissue is present inside the abdominal cavity (intraabdominal fat). Based on magnetic resonance imaging (MRI), it has been estimated that the men and women may contain about 15–18% and 7– 8% of their total body fat, respectively within the abdominal cavity (10). In contrast, only minor amounts of body fat are contained within the thoracic cavity. The intraabdominal adipose tissue can be further subdivided into ip and retroperitoneal adipose tissue compartments. The venous drainage of the ip adipose tissue is unique; it drains directly into the liver through the portal vein compared with the retroperitoneal adipose tissue, which drains into the systemic circulation. Thus, it is likely that free fatty acids (FFA), glycerol and other adipocytokines released from the ip adipose tissue may have peculiar effects on hepatic metabolism of glucose, triglycerides, insulin, and other substrates and hormones. Another clear anatomical distinction exists between the sc adipose tissue located centrally in the truncal region and that in the peripheral region in the upper and lower extremities and in the hips. Although both the central and peripheral sc adipose tissue depots drain into the systemic circulation, accumulation of fat in these depots may confer different susceptibilities to developing insulin resistance. The total amount of fat present in the truncal region, called truncal fat, constitutes both the intraabdominal and intrathoracic fat depots as well as sc fat present in the thoracic and abdominal regions.