Postprandial triglyceride-rich lipoprotein metabolism and insulin sensitivity in nonalcoholic steatohepatitis patients

Nonalcoholic steatohepatitis (NASH) is a syndrome frequently associated wit h obesity, diabetes mellitus, and dyslipidemia. Increased fasting insulinem ia and blood glucose levels may trigger a reduced catabolism of lipoprotein s rich in triglycerides by lipoprotein lipase (LPL) and an increase in thei r fasting and postprandial levels. An association between postprandial lipe mia and coronary heart disease has been observed, and many studies now supp ort this concept. The most important result of our study is the increase in triglyceride-rich lipoproteins response after a fat load in NASH patients, the increase of incremental area under the postprandial curve, an the dura tion of the hypertriglyceridemic peaks. The persisting postprandial plasma triglyceride elevation in NASH patients was mostly due to the elevated plas ma level of large triglyceride-rich particles. These data are coupled with lower plasma HDL2-cholesterol levels. As for lipoprotein analyses, the numb er of apolipoprotein B100 (ApoB100) particles is not significantly differen t between the two groups, and the higher content of triglycerides in NASH v ery low density lipoproteins (VLDL) increases the triglyceride-to-ApoB rati o and the particle size. A decreased enzymatic activity of LPL or a defecti ve assembly and secretion of VLDL from hepatocytes due to a moderate reduct ion in microsomal triglyceride transfer protein could be involved in the ov erloading of VLDL. Moreover, the undetectable levels of ApoB48 in triglycer ide-rich lipoproteins fraction A could be related to the synthesis of small er and denser chylomicrons. NASH patients not only are insulin resistant bu t also tend to present alterations in fatty meal delivery, suggesting that an increase in fasting plasma insulin and glucose, with insulin resistance, joins with depressed metabolism of triglyceride-rich lipoproteins. An incr ease in postprandial triglyceride levels with production of large VLDL sugg ests an atherogenic behavior of lipid metabolism, in accordance with the hi gh prevalence of the metabolic syndrome in NASH patients. This paper sugges ts that a fat load may be useful in early detection of atherogenic risk in the presence of otherwise normal fasting plasma lipids.