L-FABP T94A is associated with fasting triglycerides and LDL-cholesterol in women

Fisher, Eva; Weikert, Cornelia; Klapper, Maja; Lindner, Inka; Möhlig, Matthias; Spranger, Joachim; Boeing, Heiner; Schrezenmeir, Jürgen; Döring, Frank

doi:10.1016/j.ymgme.2007.03.002

Cited by 54 publications

(72 citation statements)

References 25 publications

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“…Both lines of mice exhibit some similar phenotypes with the human FABP1 T94A variants, such as defective hepatic fatty acid uptake, oxidation, VLDL secretion, and triglyceride metabolism ( 100,(104)(105)(106)(107)(108)(109)(110). However, results of studies on the roles of FABP1 in obesity and by guest, on May 10, 2018 www.jlr.org Downloaded from models.…”

Section: For Example Fabp1mentioning

confidence: 99%

Recent insights into the biological functions of liver fatty acid binding protein 1

Wang

Bonkovsky

Lemos

et al. 2015

Journal of Lipid Research

194

175

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Section: For Example Fabp1mentioning

confidence: 99%

Recent insights into the biological functions of liver fatty acid binding protein 1

Wang

Bonkovsky

Lemos

et al. 2015

Journal of Lipid Research

194

175

View full text Add to dashboard Cite

“…For example, human variants in the L-FABP gene exhibit elevated fasting LDL-cholesterol and triglyceride levels-traits associated with increased risk of CVD, type 2 diabetes, and metabolic syndrome ( 35,36 ). This phenotype was exacerbated by treatment with fenofi brate ( 36 ).…”

Section: Immunoelectron Microscopy Of Fi Xed Hepatocytes: Direct L-famentioning

confidence: 99%

L-FABP directly interacts with PPARα in cultured primary hepatocytes

Hostetler

McIntosh

Atshaves

et al. 2009

Journal of Lipid Research

133

129

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“…Therapeutic interest in L-FABP has increasingly focused on L-FABP's protection against hepatocellular oxidative stress, as in diabetes (56,76,77,85), and on developing fibrate analogs better bound and targeted by L-FABP for activating PPAR␣ (13,62,82). Part of this interest is based on the discovery of the L-FABP T94A variant, which is the most frequently occurring polymorphism in the entire FABP protein family, with a 26 -38% minor allele frequency (8.3 ϩ 1.9% frequency of homozygous variant) in multiple populations tested worldwide [mutation annotation format for 1,000 genomes in National Center for Biotechnology Information singlenucleotide polymorphism database; ALFRED database] (11,18,38,54,61,80,84). The human L-FABP T94A variant is Values are means Ϯ SE (n ϭ 3).…”

Section: Effects Of Extracellular Glucose Concentration On [ 3 H]steamentioning

confidence: 99%

“…The human L-FABP T94A variant is Values are means Ϯ SE (n ϭ 3). associated with high plasma triglyceride (10,18) and high LDL cholesterol (18,54), features associated with increased risk of CVD and type 2 diabetes (10, 18). It has been suggested that the L-FABP null mouse has a phenotype similar to that of humans with the L-FABP T94A polymorphism (10,18).…”

Section: Effects Of Extracellular Glucose Concentration On [ 3 H]steamentioning

confidence: 99%

Loss of intracellular lipid binding proteins differentially impacts saturated fatty acid uptake and nuclear targeting in mouse hepatocytes

Storey

McIntosh

Huang

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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-The liver expresses high levels of two proteins with high affinity for long-chain fatty acids (LCFAs): liver fatty acid binding protein (L-FABP) and sterol carrier protein-2 (SCP-2). Real-time confocal microscopy of cultured primary hepatocytes from gene-ablated (L-FABP, SCP-2/ SCP-x, and L-FABP/SCP-2/SCP-x null) mice showed that the loss of L-FABP reduced cellular uptake of 12-N-methyl-(7-nitrobenz-2-oxa-1,3-diazo)-aminostearic acid (a fluorescent-saturated LCFA analog) by ϳ50%. Importantly, nuclear targeting of the LCFA was enhanced when L-FABP was upregulated (SCP-2/SCP-x null) but was significantly reduced when L-FABP was ablated (L-FABP null), thus impacting LCFA nuclear targeting. These effects were not associated with a net decrease in expression of key membrane proteins involved in LCFA or glucose transport. Since hepatic LCFA uptake and metabolism are closely linked to glucose uptake, the effect of glucose on L-FABP-mediated LCFA uptake and nuclear targeting was examined. Increasing concentrations of glucose decreased cellular LCFA uptake and even more extensively decreased LCFA nuclear targeting. Loss of L-FABP exacerbated the decrease in LCFA nuclear targeting, while loss of SCP-2 reduced the glucose effect, resulting in enhanced LCFA nuclear targeting compared with control. Simply, ablation of L-FABP decreases LCFA uptake and even more extensively decreases its nuclear targeting. liver fatty acid binding protein; sterol carrier protein-2; glucose HEPATIC LONG-CHAIN FATTY ACIDS (LCFAs) and glucose are metabolically linked through the intracellular LCFA pool arising from exogenous (dietary) uptake and de novo synthesis from glucose. High blood levels of LCFAs, as well as glucose, are significant risk factors in the pathogenesis of diabetes and associated cardiovascular disease (CVD) (87). The liver plays a major role in maintaining blood LCFA, as well as glucose, homeostasis (64). Exogenous LCFAs are translocated into the hepatocyte via bifunctional membrane-bound fatty acid transport proteins (FATPs) with acyl-coenzyme A (CoA) synthase activity (FATP2, FATP4, and FATP5) (reviewed in Ref. 78). The liver contains high levels of two soluble proteins, liver fatty acid binding protein (L-FABP) and sterol carrier protein-2 (SCP-2), with high affinity for LCFA, as well as LCFA-CoA (reviewed in Refs. 19,20,52,59,82).The impact of L-FABP and SCP-2 on LCFA uptake has been examined in transformed cell lines and in L-FABP genetargeted mice. Overexpression of L-FABP in L-cell fibroblasts, cells with a very low level of endogenous FABP or SCP-2, enhanced cellular LCFA uptake (7, 49). While L-FABP antisense treatment of HepG2 hepatoma cells decreased cellular LCFA uptake, such hepatoma cells normally express 3-to 10-fold less L-FABP and SCP-2 than the liver (34, 83). This issue was resolved with L-FABP null mice, which exhibit decreased hepatic LCFA uptake in vivo (40, 51). SCP-2 overexpression in L-cell fibroblasts also enhanced LCFA uptake (8,48). Conversely, nothing is known about the effect of SCP-2 gene ablati...

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L-FABP T94A is associated with fasting triglycerides and LDL-cholesterol in women

Cited by 54 publications

References 25 publications

Recent insights into the biological functions of liver fatty acid binding protein 1

Recent insights into the biological functions of liver fatty acid binding protein 1

L-FABP directly interacts with PPARα in cultured primary hepatocytes

Loss of intracellular lipid binding proteins differentially impacts saturated fatty acid uptake and nuclear targeting in mouse hepatocytes

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