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Review
. 2013 May 10;5(5):1544-60.
doi: 10.3390/nu5051544.

Non-alcoholic fatty liver disease (NAFLD) and its connection with insulin resistance, dyslipidemia, atherosclerosis and coronary heart disease

Melania Gaggini  1 , Mariangela Morelli, Emma Buzzigoli, Ralph A DeFronzo, Elisabetta Bugianesi, Amalia Gastaldelli
Affiliations
Review

Non-alcoholic fatty liver disease (NAFLD) and its connection with insulin resistance, dyslipidemia, atherosclerosis and coronary heart disease

Melania Gaggini et al. Nutrients. .

Abstract

Non-alcoholic fatty liver disease is marked by hepatic fat accumulation not due to alcohol abuse. Several studies have demonstrated that NAFLD is associated with insulin resistance leading to a resistance in the antilipolytic effect of insulin in the adipose tissue with an increase of free fatty acids (FFAs). The increase of FFAs induces mitochondrial dysfunction and development of lipotoxicity. Moreover, in subjects with NAFLD, ectopic fat also accumulates as cardiac and pancreatic fat. In this review we analyzed the mechanisms that relate NAFLD with metabolic syndrome and dyslipidemia and its association with the development and progression of cardiovascular disease.

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Figures

Figure 1
Figure 1
Non-alcoholic fatty liver disease (NAFLD) is not a primary determinant of insulin resistance, since subjects with hepatic TG accumulation due to genetic predisposition have a degree of hepatic and/or peripheral insulin resistance comparable to subjects without mutation.
Figure 2
Figure 2
Right panel: Insulin resistance at the level of liver, muscle and adipose tissue is increased proportionally to both IH-TG and VF. Data redrawn from [7]. Average data for IH-TG and VF are shown in Table 1. Left panel: Subjects with similar but high VF (~1.3 kg) had increased insulin resistance if they had high IH-TG (~25%) compared to subjects with low IH-TG (4%) [12]. However, when matched per IH-TG (~13%), subjects with low and high VF had comparable indexes of insulin resistance (reproduced with permission from [12]).
Figure 3
Figure 3
Similar correlations between liver and visceral fat accumulation, hepatic insulin resistance (i.e., the resistance to the effect of insulin to reduce fasting hepatic glucose production), top panels A and B, and between liver and visceral fat and hepatic insulin clearance, bottom panels C and D. Data redrawn from [7].
Figure 4
Figure 4
Link between insulin resistance and metabolic dyslipidemia. Insulin resistance is associated with an increase of free fatty acids (FFAs) flux that contributes to increased TG production that, in turn, stimulate assembly and secretion of VLDL in hepatocytes. Fat accumulation in the liver is associated with oxidative stress and lipid peroxidation. Furthermore NAFLD subjects have increased secretion of inflammatory markers, plasma glucose and a decrease in HDL concentration. The consequence of this physiological dysfunction is increased risk for the development of diabetes and atherosclerosis and increased risk for coronary artery disease.
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