BACKGROUND: The -493G/T polymorphism in the microsomal triglyceride transfer protein (MTP) gene is associated with lower serum low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels and longevity in several populations, but the results are inconsistent in different racial/ethnic groups. The current study was to investigate the plausible association of MTP -493G/T polymorphism with serum lipid levels and longevity in Zhuang long-lived families residing in Bama area, a famous home of longevity in Guangxi, China.
Familial forms of isolated hypercholesterolemia are inherited autosomal-dominantly and are caused by defects of the low-density lipoprotein (LDL) receptor protein or its ligand, the apolipoprotein B-100, the exclusive apolipoprotein moiety of the LDL particles. Mutations at the LDL receptor gene locus (more than 150 different mutations have been described up to now) lead to familial hypercholesterolemia (FH); the only mutation at the apolipoprotein B-100 gene locus described in detail so far leads to the so-called familial defective apolipoprotein B-100 (FDB).
Arteriosclerosis, Thrombosis, and Vascular Biology
OBJECTIVE: Hypercholesterolemia is a major risk factor for coronary artery disease. Therapeutic lifestyle changes include dietary modifications such as inclusion of phytosterols, which effectively lowers low-density lipoprotein (LDL) cholesterol in margarines and other fats. Their effectiveness in nonfat moieties is not yet established. The aim of this study was to examine if phytosterols alter the plasma lipoprotein profile when incorporated into nonfat orange juice.
The cardioprotective effect of consuming cruciferous vegetables may be attributed to a number of unique indole-based compounds. We investigated the potential role and mechanism of action of an indole-based compound, indole-3-carbinol (I-3-C), on apolipoprotein B-100 (apoB) production using HepG2 cells. I-3-C reduced apoB secretion into the media dose dependently by 56% at 100 micromol/L. Relative to the untreated control cells, no change in the density of the secreted lipoproteins was noted.
OBJECTIVE: We hypothesized that simvastatin may reduce adiponectin levels and insulin sensitivity in hypercholesterolemic patients. RESEARCH DESIGN AND METHODS: This was a randomized, double-blind, placebo-controlled, parallel study. Age, sex, and BMI were matched. Thirty-two patients were given placebo, and 30, 32, 31, and 31 patients were given daily 10, 20, 40, and 80 mg simvastatin, respectively, during a 2-month treatment period.
Fructose consumption in the USA has increased over the past three decades. During this time, obesity, insulin resistance and the metabolic syndrome have also increased in prevalence. While diets high in fructose have been shown to promote insulin resistance and increase TAG concentrations in animals, there are insufficient data available regarding the long-term metabolic effects of fructose consumption in humans.
The atheroprotective potential of n-3 alpha-linolenic acid (ALA) has not yet been fully determined, even in murine models of atherosclerosis. We tested whether ALA-derived, n-3 long chain polyunsaturated fatty acids (LCPUFA) could offer atheroprotection in a dose-dependent manner. Apolipoprotein B (ApoB)100/100LDLr-/- mice were fed with diets containing two levels of ALA from flaxseed oil for 16 weeks. Fish oil- and cis-monounsaturated-fat-enriched diets were used as positive and negative controls, respectively.
Loss of ABCA1 activity in Tangier disease (TD) is associated with abnormal apoB lipoprotein (Lp) metabolism in addition to the complete absence of high density lipoprotein (HDL). We used hepatocyte-specific ABCA1 knock-out (HSKO) mice to test the hypothesis that hepatic ABCA1 plays dual roles in regulating Lp metabolism and nascent HDL formation. HSKO mice recapitulated the TD lipid phenotype with postprandial hypertriglyceridemia, markedly decreased LDL, and near absence of HDL.
In Tangier disease, absence of ATP binding cassette transporter A1 (ABCA1) results in reduced plasma HDL and elevated triglyceride (TG) levels. We hypothesized that hepatocyte ABCA1 regulates VLDL TG secretion through nascent HDL production. Silencing of ABCA1 expression in oleate-stimulated rat hepatoma cells resulted in: 1) decreased large nascent HDL (>10 nm diameter) and increased small nascent HDL (<10 nm) formation, 2) increased large buoyant VLDL1 particle secretion, and 3) decreased phosphatidylinositol-3 (PI3) kinase activation.
Very low-density lipoprotein (VLDL) secretion provides a mechanism to export triglycerides (TG) from the liver to peripheral tissues, maintaining lipid homeostasis. In nonalcoholic fatty liver disease (NAFLD), VLDL secretion disturbances are unclear. Methionine adenosyltransferase (MAT) is responsible for S-adenosylmethionine (SAMe) synthesis and MAT I and III are the products of the MAT1A gene. Deficient MAT I and III activities and SAMe content in the liver have been associated with NAFLD, but whether MAT1A is required for normal VLDL assembly remains unknown.