Insulin Resistance in the Control of Body Fat Distribution: A New Hypothesis

Abstract

Obesity causes insulin resistance, which is a prime etiological factor for type 2 diabetes, dyslipidemia, and cardiovascular disease. However, insulin resistance may be a normal physiological response to obesity that limits further fat deposition and which only has pathological effects at high levels. The current hypothesis suggests that in obesity the initial deposition of triglycerides occurs in subcutaneous adipose tissue and as this increases in size insulin resistance will rise and limit further subcutaneous lipid accumulation. Triglycerides will then be diverted to the visceral fat depot as well as to ectopic sites. This leads to a substantial rise in insulin resistance and the prevalence of its associated disorders. Evidence supporting this hypothesis includes studies showing that in lean subjects the prime determinant of insulin resistance is BMI, that is, subcutaneous fat whilst in overweight and obese subjects it is waist circumference and visceral adiposity. It has also been shown that the metabolic syndrome suddenly increases in prevalence at high levels of insulin resistance and we suggest that this is due to the diversion of lipids from the subcutaneous to the visceral depot. This system may have functioned in our evolutionary past to limit excessive adiposity by causing lipid deposition to occur at a site that has maximal effects on insulin resistance but involves minimal weight gain.

Inflammatory stress induces lipid accumulation in multi-organs of <italic>db</italic>/<italic>db</italic> mice

“…Under physiological conditions, excessive free fatty acid is converted to TG or cholesteryl ester to be stored in adipocyte lipid droplets [14]. The initial deposition of TGs occurs in subcutaneous adipose tissue, and as the deposition increases in size, insulin resistance increases, which limits further subcutaneous lipid accumulation [15]. Lipids are then diverted to visceral fat depots and nonadipose tissue, which is also known as ectopic lipid accumulation or lipid redistribution [16,17].…”

Gestational Diabetes and the Offspring: Implications in the Development of the Cardiorenal Metabolic Syndrome in Offspring

“…Added fat mass may then lead to insulin and leptin resistance in these infants [39]. One group compared treatment of GDM with metformin or with insulin by looking at the body composition of the offspring at 2 years of age [40].…”

Insulin Resistance Predicts the Effectiveness of Different Glycemic Index Diets on Weight Loss in Non-Obese Women

“…Our sample has the important characteristic of a similar overall adiposity (measured by BMI) in both IR groups but greater difference in waist circumference. The subcutaneous adipose depot is the primary store site for fat, and an enlargement of subcutaneous fat depot leads to an increase of IR, limiting lipid deposition at the subcutaneous site and leading to an increased uptake of triglycerides in the visceral adipose depot [25,26]. In our study, the IR group had greater waist circumference and waist-to-hip ratio (a surrogate for visceral fat), and studies have been showing that visceral adipose tissue is more resistant to antilipolytic effects of insulin than subcutaneous fat [27].…”