Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Based on titration microcalorimetry and Caco-2 cell line transfection studies, it has been suggested that the A54T of the FABP2 gene plays a significant role in the assimilation of dietary fatty acids. However, reports were divergent with regard to the in vivo interaction between this polymorphism and postprandial lipemia. We therefore determined the influence of this intestinal fatty acid-binding protein polymorphism on intestinal fat transport using the human jejunal organ culture model, thus avoiding the interference of various circulating factors capable of metabolizing in vivo postprandial lipids. Analysis of DNA samples from 32 fetal intestines revealed 22 homozygotes for the wild-type Ala-54/Ala-54 genotype (0.83) and 10 heterozygotes for the polymorphic Thr-54/Ala-54 genotype (0.17). The Thr-encoding allele was associated with increased secretion of newly esterified triglycerides, augmented de novo apolipoprotein B synthesis, and elevated chylomicron output. On the other hand, no alterations were found in very low density lipoprotein and high density lipoprotein production, apolipoprotein A-I biogenesis, or microsomal triglyceride transfer protein mass and activity. Similarly, the alanine to threonine substitution at residue 54 did not result in changes in brush border hydrolytic activities (sucrase, glucoamylase, lactase, and alkaline phosphatase) or in glucose uptake or oxidation. Our data clearly document that the A54T polymorphism of FABP2 specifically influences small intestinal lipid absorption without modifying glucose uptake or metabolism. It is proposed that, in the absence of confounding factors such as environmental and genetic variables, the FABP2 polymorphism has an important effect on postprandial lipids in vivo, potentially influencing plasma levels of lipids and atherogenesis.
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PMID:The polymorphism at codon 54 of the FABP2 gene increases fat absorption in human intestinal explants. 1148 82

The present study was performed to investigate the effects of the intestinal fatty acid-binding protein (FABP2) gene Ala54Thr polymorphism and the beta(3)-adrenergic receptor (beta3AR) gene Trp64Arg polymorphism on body mass index (BMI), blood pressure, heart rate, glucose and lipid profiles, and serum leptin level in 196 young men aged 21 to 39 years, 186 older normoglycemic men (fasting plasma glucose [FPG] < 110 mg/dL) aged 40 to 65 years, and 122 older hyperglycemic men, including 77 type 2 diabetic patients. Genomic DNA was extracted from the peripheral blood, and these polymorphisms were assessed by the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. In the older groups, the beta3AR Arg64-allele frequency tended to be lower and the FABP2 Thr/Thr54 genotype frequency tended to be higher in hyperglycemic patients, although these differences did not reach statistical significance. Also, there were no significant differences in the genotype or allele frequency of either variant between the 27 hyperlipidemic and 204 normolipidemic subjects. In the younger group, there were no significant differences in any of the parameters measured between the genotypes of beta3AR or FABP2. In the older normoglycemic subjects, heart rate was significantly lower (P =.037) in beta3AR Arg64-positive subjects, and FPG was significantly higher in subjects with the FABP2 Thr/Thr genotype than the other genotypes (99.8 +/- 5.6 v 96.5 +/- 5.6 mg/dL, P =.010). In the older hyperglycemic group, the beta3AR Arg64-positive group had significantly lower high-density lipoprotein (HDL) cholesterol and free fatty acid (FFA) levels (P =.024 and P =.043, respectively). There were no synergistic effects of these 2 variants on any measured parameter, but only the FABP2 Thr/Thr genotype was related to a higher FPG in the older normoglycemic men. In conclusion, no major difference was associated with the beta3AR Trp64Arg or FABP2 Ala54Thr polymorphism in terms of type 2 diabetes or hyperlipidemia in young to older Japanese men. However, a slight but significant increase in FPG was observed in older Japanese men with the FABP2 Thr/Thr genotype.
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PMID:Effects of intestinal fatty acid-binding protein gene Ala54Thr polymorphism and beta3-adrenergic receptor gene Trp64Arg polymorphism on insulin resistance and fasting plasma glucose in young to older Japanese men. 1169 48

Familial combined hyperlipidemia (FCHL) is a common, atherogenic lipid disorder characterized by a variable phenotypic expression of hyperlipidemia. Variations in genes regulating fatty acid metabolism must be considered in the search for factors affecting the lipid phenotypic expression of FCHL. Therefore, we have evaluated the association of the common variants in the lipoprotein lipase (LPL) (D9N, N291S, and S447X), insulin receptor substrate-1 (IRS-1) (G972R), fatty acid binding protein-2 (FABP-2) (A54T), and beta3-adrenergic receptor (beta3-AR) (W64R) genes with lipid and lipoprotein levels in 30 Italian FCHL families (195 individuals). The transmission disequilibriun test (TDT) was used to evaluate the association between these variants and the FCHL trait. No significant differences were observed in the frequencies of the common LPL variants between affected and nonaffected FCHL family members. A significantly lower frequency of the LPL447X allele was noted only when members of the FCHL families were compared with normolipemic controls (.06 v.142, respectively; P <.01) suggesting a reduced representation of this LPL variant in FCHL families. The frequencies of variants in the IRS-1, FABP-2, and beta3-AR genes were not significantly different between affected and nonaffected FCHL family members and normolipemic controls. The TDT did not demonstrate any significant association of these gene variants with the FCHL trait. FCHL individuals carrying the LPL N291S gene showed higher plasma lipids and apolipoprotein B (apoB) levels compared with affected noncarriers. Only a marginal effect of the LPL D9N and S447X variants on lipid levels in FCHL individuals was observed. Conversely, the variants in the IRS-1, FABP2, and beta3-AR genes did not show any major influence on lipid and lipoprotein levels in FCHL family members. In conclusion, these results confirmed that none of the investigated genes were major loci for FCHL. Nevertheless, variations in genes affecting the removal rate of triglycerides (TG) from plasma, such as the LPL gene, significantly influence the lipid phenotypic expression of FCHL. Conversely, genetic variants in the IRS-1, FABP-2, and the beta3-AR gene appear not to have a major role as modifier genes in FCHL.
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PMID:Common variants in the lipoprotein lipase gene, but not those in the insulin receptor substrate-1, the beta3-adrenergic receptor, and the intestinal fatty acid binding protein-2 genes, influence the lipid phenotypic expression in familial combined hyperlipidemia. 1237 Aug 50

People spend a large percentage of their waking hours in the postprandial state. Postprandial lipemia is associated with disruptions in lipoprotein metabolism and inflammatory factors, cardiovascular disease, MetS, and diabetes. Commonly, the dietary sources of fat exceed the actual needs and the tissues are faced with the excess, with accumulation of chylomicrons and remnant particles. This review will summarize recent findings in postprandial lipemia research with a focus on human studies. The effects of dietary factors and other meal components on postprandial lipemia leads to the following question: do we need a standardized oral lipid tolerance test (OLTT)? An overview of recent findings on FABP2, MTP, LPL, apoAV, and ASP and the effects of body habitus (sex influence and body size), as well as exercise and weight loss, on postprandial lipemia will be summarized.
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PMID:Regulation of postprandial lipemia: an update on current trends. 1733 85

Various dietary factors affect postprandial metabolism yet precise mechanisms have not necessarily been pinpointed. The effects of various meal components on postprandial lipemia lead to the following question: do we need a standardized oral lipid tolerance test? A number of transporters, enzymes, receptors and hormones directly influence and act as "gatekeepers" of these processes. Each protein appears to have specific and individual functional roles in the overall process and selected developments in these areas will be reviewed. Within the intestinal cells, FABP2 (fatty acid-binding protein 2) and MTP (microsomal triglyceride transfer protein) are required for the formation of chylomicrons. Niemann-Pick C1-like 1 (NPC1-L1) plays an important role in cholesterol absorption and provides a pharmacological target. Hormones such as GLP1 and GLP2 influence this absorption process. Within the periphery, lipoprotein lipase (LPL) is a key gatekeeper of clearance. Of the massive amounts of fatty acids released by LPL, 36% escape peripheral adipose and muscle uptake and fatty acid overload can result in LPL product inhibition. Acylation stimulating protein (ASP) and insulin are two key hormones in maintaining efficient tissue uptake and re-esterification of fatty acids while TNFalpha negatively influences this process. In both ASP deficient (C3 KO) and C5L2 KO mice, postprandial lipemia increased with reduced adipose tissue storage. This is compensated by increased energy expenditure and muscle lipid oxidation. Clearance of hepatic remnants is controlled through many factors, including SR-B1 and ABCA1. Intestinal, peripheral and hepatic gatekeepers serve important and individual roles in regulating postprandial lipemia and provide potential targets for regulation.
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PMID:Intestinally derived lipids: metabolic regulation and consequences--an overview. 1869 44