Ectopic fat and insulin resistance: pathophysiology and effect of diet and lifestyle interventions

Abstract

The storage of triglyceride (TG) droplets in nonadipose tissues is called ectopic fat storage. Ectopic fat is associated with insulin resistance and type 2 diabetes mellitus (T2DM). Not the triglycerides per se but the accumulation of intermediates of lipid metabolism in organs, such as the liver, skeletal muscle, and heart seem to disrupt metabolic processes and impair organ function. We describe the mechanisms of ectopic fat depositions in the liver, skeletal muscle, and in and around the heart and the consequences for each organs function. In addition, we systematically reviewed the literature for the effects of diet-induced weight loss and exercise on ectopic fat depositions.

Figure 1

Ectopic fat depositions. Gene-environment interactions might be involved both in increased energy intake and decreased physical activity as well as in the response of adipose tissue to the ensuing increased energy balanced. Predisposed subjects will elicit a pathophysiologic response leading to adipocyte hypertrophy. This will lead to an inflammatory response that ultimately leads to ectopic fat deposition. The consequences of ectopic fat are organ specific as depicted in this figure. The effect of ectopic fat on the cellular level is different and depicted in Figure 2. FFAs: free fatty acids; EGP: endogenous glucose production; VLDL-TG: very low-density lipoprotein-triglyceride.

Figure 2

(a) cellular processes leading to insulin resistance in the skeletal muscle cell; (b) cellular processes leading to insulin resistance in the liver cell; (c) cellular processes in the cardiomyocyte leading to myocardial dysfunction.

Figure 3

Four-chamber view of the heart. Four-chamber view of the heart where the signal from blood and muscle are suppressed. E: epicardial fat; P: pericardial fat.