General Adiposity
Samuel Klein, MD
The precise relationship between individual abdominal fat depots and insulin resistance is not clear. Studies of the role of increased visceral fat as a cause of insulin resistance have yielded variable results. Imprecision in the measurement of body fat depots and real biologic variation in lipolytic activity of fat depots may both play a role. Visceral fat appears to have a very small role in the oversupply of free fatty acids to extrahepatic tissues in insulin-resistant states. Subcutaneous fat, especially in the upper body, is the major contributor to this mediator of insulin resistance.
Increases in visceral fat mass, even among normal-weight persons, are accompanied by increases in subcutaneous fat mass. Thus, visceral fat may be responsible for hepatic insulin resistance in some circumstances but is no more than a marker for insulin resistance in extrahepatic tissues. Future studies should focus on the relationship between upper-body subcutaneous and visceral fat depots, regulation of free fatty acid metabolism, and the relative contribution of insulin resistance in liver versus that in skeletal muscle to systemic insulin resistance.
Visceral Adiposity
Jean-Pierre Després, PhD
Although the visceral adipose tissue depot is much smaller than the total subcutaneous adipose tissue depot or total adiposity, many studies show that the visceral adipose tissue mass, and not the subcutaneous or total adipose tissue mass, is significantly correlated in multivariate analyses with insulin resistance, type 2 diabetes, and cardiovascular events. The hypothesis that visceral adiposity and not total adiposity was the cause of the components and clinical consequences of the metabolic syndrome has been challenged in studies showing either that abdominal subcutaneous adipose tissue mass and not visceral adipose tissue mass was independently correlated with insulin resistance or that they were both equally correlated. Studies using isotopic techniques show that most circulating free fatty acids are derived from peripheral adipose tissue. If free fatty acids are responsible for the insulin resistance associated with obesity, then total adiposity rather than visceral adiposity should be responsible for insulin resistance.
Several lines of evidence support the hypothesis that visceral adipose tissue, and not subcutaneous adipose tissue, is the major contributor in causing insulin resistance and the metabolic syndrome.
Absence of insulin resistance in overweight and obese individuals with lower body obesity. Individuals with lower body obesity have an increase in total adiposity that is predominately in subcutaneous adipose tissue; visceral adipose tissue is not significantly affected.
Correlation between adipose tissue depots and insulin resistance. Studies show that visceral adiposity, in a variety of populations, is associated with and predicts the development of type 2 diabetes, coronary heart disease, and hypertension. Dr. Després’ group showed that visceral adiposity is the component of adiposity that is the independent risk factor for insulin resistance, glucose intolerance, and cardiovascular risk factors.
In obese children and adolescents with impaired glucose tolerance, intramyocellular and visceral lipid deposits are increased and the abdominal subcutaneous adipose tissue depot is decreased, as indicated by magnetic resonance imaging. These abnormalities are associated with the development of severe peripheral insulin resistance.
Liposuction removal of abdominal subcutaneous adipose tissue in obese nondiabetic and type 2 diabetic subjects. Studies have shown that the removal of the abdominal subcutaneous fat had no effect on insulin resistance, plasma glucose or insulin levels, plasma adiponectin levels, or any of the lipid or inflammatory components of the metabolic syndrome.
Thiazolidinediones increase abdominal subcutaneous adipose tissue mass but decrease insulin resistance and improve most of the components of the metabolic syndrome. Pioglitazone, rosiglitazone, and troglitazone have been shown to increase total body fat and abdominal subcutaneous adipose tissue while having no effect on or slightly decreasing visceral adipose tissue. Despite this increase in overall obesity, the thiazolidinediones improve insulin sensitivity and all of the components of the metabolic syndrome. Plasma free fatty acid levels decrease 20%-25%, and hepatic fat decreases 25%-50%.
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