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

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Lipids

Abstract

Nonalcoholic steatohepatitis (NASH) is a syndrome frequently associated with obesity, diabetes mellitus, and dyslipidemia. Increased fasting insulinemia and blood glucose levels may trigger a reduced catabolism of lipoproteins rich in triglycerides by lipoprotein lipase (LPL) and an increase in their fasting and postprandial levels. An association between postprandial lipemia and coronary heart disease has been observed, and many studies now support 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, and the duration of the hypertriglyceridemic peaks. The persisting postprandial plasma triglyceride elevation in NASH patients was mostly due to the elevated plasma level of large triglyceride-rich particles. These data are coupled with lower plasma HDL2-cholesterol levels. As for lipoprotein analyses, the number of apolipoprotein B100 (ApoB100) particles is not significantly different between the two groups, and the higher content of triglycerides in NASH very low density lipoproteins (VLDL) increases the triglyceride-to-ApoB ratio and the particle size. A decreased enzymatic activity of LPL or a defective assembly and secretion of VLDL from hepatocytes due to a moderate reduction in microsomal triglyceride transfer protein could be involved in the overloading of VLDL. Moreover, the undetectable levels of ApoB48 in triglyceride-rich lipoproteins fraction A could be related to the synthesis of smaller and denser chylomicrons. NASH patients not only are insulin resistant but 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 increase in postprandial triglyceride levels with production of large VLDL suggests an atherogenic behavior of lipid metabolism, in accordance with the high prevalence of the metabolic syndrome in NASH patients. This paper suggests that a fat load may be useful in early detection of atherogenic risk in the presence of otherwise normal fasting plasma lipids.

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Abbreviations

Apo:

apolipoprotein

AUC:

area under the postprandial triglyceride curve

BMI:

body mass index

Chol:

cholesterol

FFA:

free fatty acid

FPG:

fasting plasma glucose

FSIGT:

frequently sampled intravenous glucose tolerance test

HDL:

high density lipoproteins

LDL:

low density lipoproteins

LPL:

lipoprotein lipase

MTP:

microsomal triglyceride transfer protein

NASH:

nonalcoholic steatohepatitis

OFL:

oral fat load

PCR:

polymerase chain reaction

SDS:

sodium dodecyl sulfate

Sf:

Svedberg flotation rate

SI:

sensitivity index

Tg:

triglyceride

TRL:

triglyceride-rich lipoproteins

VLDL:

very low density lipoproteins

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Authors and Affiliations

  1. Department of Internal Medicine, University of Turin, Turin, Italy

    Maurizio Cassader, Roberto Gambino, Giovanni Musso, Nadia Depetris, Fabio Mecca, Paolo Cavallo-Perin & Gianfranco Pagano

  2. Institute of Systems Science and Biomedical Engineering, (LADSEB-CNR), Padua, Italy

    Giovanni Pacini

  3. Department of Gastroenterology, University of Turin, Corso Dogliotti 14, Turin, Italy

    Mario Rizzetto

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  1. Maurizio Cassader
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  2. Roberto Gambino
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  3. Giovanni Musso
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Correspondence to Maurizio Cassader.

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Cassader, M., Gambino, R., Musso, G. et al. Postprandial triglyceride-rich lipoprotein metabolism and insulin sensitivity in nonalcoholic steatohepatitis patients. Lipids 36, 1117–1124 (2001). https://doi.org/10.1007/s11745-001-0822-5

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  • DOI: https://doi.org/10.1007/s11745-001-0822-5

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