Postprandial triglyceride-rich lipoprotein metabolism and insulin sensitivity in nonalcoholic steatohepatitis patients
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.
Article: Hydroxypropyl methylcellulose, a viscous soluble fiber, reduces insulin resistance and decreases fatty liver in Zucker Diabetic Fatty rats.[show abstract] [hide abstract]
ABSTRACT: BACKGROUND: Diets producing a high glycemic response result in exaggerated insulin secretion which induces hepatic lipogenesis, contributing to development of insulin resistance and fatty liver. Viscous dietary fibers blunt the postprandial rise in blood glucose, however their effect on type 2 diabetes and obesity are not entirely known. This study examined the effect of chronic consumption of the viscous, non-fermentable dietary fiber, hydroxypropyl methylcellulose (HPMC), on glucose control, insulin resistance and liver lipids in an obese diabetic rat model. METHODS: Three groups of Zucker Diabetic Fatty (ZDF) rats were fed diets containing either 5% nonviscous cellulose (control), low viscosity HPMC (LV-HPMC) or high viscosity HPMC (HVHPMC) for six weeks. Zucker lean littermates consuming cellulose served as a negative control. Markers of glucose control, including oral glucose tolerance test, glycated hemoglobin and urinary glucose, were measured as well as adiposity and the accumulation of liver lipids. RESULTS: The HPMC diets increased the viscosity of the small intestinal contents and reduced the postprandial rise in blood glucose. The food efficiency ratio was greater with HPMC feeding compared to the obese control and urinary excretion of glucose and ketone bodies was reduced. The two HPMC groups had lower glycated hemoglobin and kidney weights and a reduced area under the curve during a glucose tolerance test, indicating improved glucose control. Epididymal fat pad weight as percent of body weight was reduced in the HV-HPMC group compared to the obese control group. The HV-HPMC group also had lower concentrations of liver lipid and cholesterol and reduced liver weight. However, HV-HPMC feeding did not affect hepatic gene expression of SREBP-1c or FAS. Muscle concentration of acylcarnitines, a lipid intermediate in fatty acid beta-oxidation, was not different between the HPMC groups and obese control, suggesting no change in muscle fatty acid oxidation by HPMC. CONCLUSIONS: Consumption of the viscous non-fermentable fiber HPMC decreased diabetic wasting, improved glucose control and reduced insulin resistance and fatty liver in a model of obesity with diabetes.Nutrition & Metabolism 11/2012; 9(1):100. · 2.88 Impact Factor
Chapter: Association Between Fatty Liver and Cardiovascular Disease: Mechanism and Clinical Implications09/2011; , ISBN: 978-953-307-641-6
Article: Non-alcoholic fatty liver disease and cardiovascular disease: epidemiological, clinical and pathophysiological evidences.[show abstract] [hide abstract]
ABSTRACT: Non-alcoholic fatty liver disease is recognized as the most common and emerging chronic liver disease in western countries. The disease has been traditionally interpreted as a possibly progressing condition to liver fibrosis and cirrhosis. However, recently, a large number of publications have demonstrated that people with non-alcoholic fatty liver have an increased chance of developing cardiovascular diseases, which represent the major causes of death in this setting. This association is mainly explained by the atherogenic profile of the metabolic syndrome a condition frequently associated with fatty liver, which may represent its hepatic component. Some studies have also shown an association independent of traditional risk factors or of the clinical features of the metabolic syndrome. In this setting, cardiovascular disease seems to be the consequence of low-grade chronic inflammation and increased oxidative stress. Most studies did not differentiate cardiovascular risk between simple steatosis and non-alcoholic steatohepatitis, although the latter seems to be at higher cardiovascular risk. Few studies have investigated the direct correlation between hepatic inflammation and atherosclerosis. Genetic studies will probably improve the interpretation of the increased cardiovascular risk in patients with fatty liver and no metabolic syndrome.Internal and Emergency Medicine 10/2012; 7 Suppl 3:291-6. · 2.06 Impact Factor