Lean adolescents with insulin resistance display higher angiopoietin like protein 3, ApoC-III and chylomicron remnant dyslipidemia.

BACKGROUND: Triglyceride-rich lipoproteins (TRL: chylomicrons and VLDL) are a key component of diabetes dyslipoproteinemia and cardiovascular risk. We have shown that it is already prevalent in obese adolescents in association with lipoprotein lipase (LPL) dysregulation. Insulin resistance (IR) suffices to produce TRL dyslipoproteinemia and LPL dysfunction even in the absence of obesity. METHODS: This cross-sectional study included euglycemic adolescents between 15 and 19 y, classified in 4 groups according to BMI, HOMA-IR and fasting lipid as: metabolically healthy lean (MHL, n = 30), metabolically unhealthy lean (MUL, n = 25), metabolically healthy obese (MHO, = 30), and metabolically unhealthy obese (MUO, n = 42). RESULTS: As compared to MHL, MUL participants showed 73% higher concentrations of ApoB-48; 84% of ApoC-III; 24% ANGPTL-3; 200% of TG; 218% of VLDL-C and 238% of TG/HDL-C c, No changes were found in LPL mass. Interestingly, the differences in these parameters between MUL and MHO were not significant. CONCLUSION: Euglycemic lean adolescents with IR display TRL dyslipoproteinemia with increased inhibition of LPL as highlighted by higher concentrations of ANGPTL-3, ApoC-III and fasting chylomicron remnants (ApoB-48).

Antihyperlipidemic effect of Cyclocarya paliurus (Batal.) Iljinskaja extract and inhibition of apolipoprotein B48 overproduction in hyperlipidemic mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Cyclocarya paliurus (CP) Batal., the sole species in its genus, is a native plant to China. As a traditional Chinese folk medicine, the tree leaves have been widely used for the treatment of metabolic disorders, including hyperlipidemia, obesity, diabetes and hypertension. AIM OF THE STUDY: The study aimed to evaluate the antihyperlipidemic effect of CP ethanol extract, as well as its inhibitory activity on apolipoproteinB48 (apoB48), in normal and hyperlipidemic mice. MATERIALS AND METHODS: The antihyperlipidemic effect of CP was evaluated in hyperlipidemic mice induced by high-fat diet for 4 weeks. CP ethanol extract (0.37, 0.75 and 1.5g/kg/day) was orally administrated once daily. Lipids and antioxidant profiles, including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), together with the indices of hepatic and renal functions were examined. RT-qPCR and western blotting were used to analysis the expression levels of tumor necrosis factor (TNF-α), total- and triglyceride-rich apoB48 (TRL-apoB48), as well as the phosphorylation of the mitogen-activatein kinase (MAPK). RESULTS: CP as well as simvastatin remarkably lowered the levels of TC, TG, LDL-C and MDA, and at the same time, elevated the HDL-C, SOD and GSH-Px in high-fat diet mice. It also decreased the serum concentration of total- and TRL-apoB48 in the fasting state. CP inhibited TNF-α expression and phosphorylation level of MAPK. Furthermore, the HE staining of liver and kidney, together with hepatic and renal function analysis showed hepato- and renoprotective activities of CP. CONCLUSIONS: These results suggested that CP possesses beneficial potentials for use in treating hyperlipidemia and the underlying lipid-lowering mechanism might associate with a down-regulation of the intestinal-associated lipoprotein apoB48, which may provide evidence about its practical application for treating hyperlipidemia and its complications.

Favorable effects of ezetimibe alone or in association with simvastatin on the removal from plasma of chylomicrons in coronary heart disease subjects.

OBJECTIVE: Reductions on the clearance from plasma of chylomicrons are associated with atherosclerosis. Statins improve the removal from plasma of chylomicrons in a dose dependent manner. There is controversy whether ezetimibe modifies the plasma clearance of chylomicrons. Effects of ezetimibe alone or in combination with simvastatin were compared with low and high dose of the latter, upon the kinetics of a chylomicron-like emulsion in coronary heart disease (CHD) patients. METHODS: 25 CHD patients were randomized for treatment with ezetimibe 10 mg (group 1) or simvastatin 20 mg (group 2) with progression to ezetimibe + simvastatin 10/20 mg or simvastatin 80 mg, respectively. Kinetic studies were performed at baseline and after each treatment period of 6 weeks. The fractional catabolic rates (FCR) of the emulsion labeled with (14)C-CE and (3)H-TG, that represent respectively chylomicron remnant and triglyceride removal, were calculated. Comparisons were made by ANOVA. RESULTS: The (14)CE-FCR in group 1 were 0.005 ± 0.004, 0.011 ± 0.008 and 0.018 ± 0.005 min(-1) and in group 2 were 0.004 ± 0.003, 0.011 ± 0.008 and 0.019 ± 0.007 min(-1) respectively at baseline, after 6 and 12 weeks (p < 0.05 vs. baseline, and 6 vs. 12 weeks). The (3)H-TG-FCR in group 1 were 0.017 ± 0.011, 0.024 ± 0.011 and 0.042 ± 0.013 min(-1) and in group 2 were 0.016 ± 0.009, 0.022 ± 0.009 and 0.037 ± 0.012 min(-1) at baseline, after 6 and 12 weeks (p < 0.05 vs. baseline, and 6 vs. 12 weeks). There were no differences between groups in time. CONCLUSION: Both treatments increased similarly the removal from plasma of chylomicron and remnants in CHD patients.