Abnormal metabolism of free fatty acids in hypertriglyceridaemic men: apparent insulin resistance of adipose tissue

Abstract

Objective. There is growing evidence that endogenous hypertriglyceridaemia is frequently accompanied by a state of insulin resistance. The present study was performed to determine whether patients with primary endogenous hypertriglyceridaemia commonly have abnormalities in plasma concentrations and turnover rates of free fatty acids (FFA), which could reflect a state of insulin resistance in adipose tissue and could account for raised plasma triglycerides. Design. Hypertriglyceridaemic and normotriglyceridemic control patients underwent measurements of plasma concentrations and turnover rates of FFA. Fat weights in both groups were determined by hydrodensitometry, and fat distribution was assessed by skin-folds and measurement of waist and hip circumferences. Other measurements included plasma glucose, insulin, lipids, and lipoproteins.Subjects. Fifteen men with normal plasma triglycerides and 21 men with primary endogenous hypertriglyceridaemia were studied. Men in both groups varied in body weights and total fat weights, but total fat weights were entirely overlapping for the two groups. Waist-to-hip ratios and waist circumferences also were similar for the two groups. Results. For any total body fat content or waist circumference, most hypertriglyceridaemia patients had higher mean plasma concentrations of FFA and higher turnover rates (flux) for FFA than did normotriglyceridemic patients. Hypertriglyceridaemic patients also had higher fasting insulin concentrations for a given body fat content. In general, both FFA flux and plasma insulin levels were positively correlated with plasma concentrations of triglyceride and inversely with high density lipoprotein (HDL) cholesterol. Conclusions. These studies indicate that many patients with primary endogenous hypertriglyceridaemia have increased flux of FFA and hyperinsulinemia that cannot be explained either by increased total body fat content or by greater waist circumferences than observed in normotriglyceridemic patients.

Fasting Plasma Free Fatty Acids and Risk of Type 2 Diabetes

“…However, FFAs also provide the substrate for production of triglyceride-rich lipoproteins (29) and stimulate production of these lipoproteins in the liver (30). Thus, elevated fasting triglycerides and FFAs may both serve as markers of increased FFA flux and disordered fat storage (31). Statistical adjustment of one analyte for the other takes on uncertain meaning in this context and may represent a form of overadjustment.…”

Caffeine Can Decrease Insulin Sensitivity in Humans

“…Plasma FFA may decrease hepatic and peripheral glucose uptake and correlates negatively with insulin sensitivity (24). Also, in essential hypertension (25) and lipid disorders (26), insulin resistance has been, in part, attributed to elevated FFAs. Plasma norepinephrine was probably of minor relevance because it was only mildly elevated with caffeine, and the increase with dipyridamole was not associated with a change in insulin sensitivity.…”

Linoleic acid-induced endothelial activation

“…Increased circulating free fatty acid levels are associated with hypertriglyceridemia and obesity, which are important risk factors leading to atherosclerosis (3)(4)(5). Dietary balance of long-chain fatty acids may influence processes involving leukocyte-endothelium interactions, such as atherogenesis and inflammation (6).…”