Polymorphisms in fatty acid binding protein 5 show association with type 2 diabetes

Bu, Liming; Salto, Lorena; León, Kevin; León, Marino De

doi:10.1016/j.diabres.2011.01.005

Cited by 33 publications

(27 citation statements)

References 52 publications

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“…The next morning, the medium was removed and hepatocytes incubated for 1 h under conditions as previously described (81), except that the Williams' medium E used was commercially custom prepared to be glucose free (Life Technologies). Following addition of glucose (6,11,20 or 30 mM) and either 40 M fatty acid-free albumin alone (Alb) or in complex with 200 M AA (C20:4n-6), EPA (C20:5n-3), or DHA (C22:6n-3) prepared as described earlier (112), the hepatocytes were incubated for an additional 5 h, medium was removed, and RNA was isolated (see Quantitative real-time PCR). The choice of glucose concentrations was based on those in mouse serum under a variety of physiological and pathological conditions: 5-6 mM as in normal mice after overnight fast; 9 -11 mM as in transient normal (after a meal) or diabetic; 14 -25 mM as in overnight-fasted high-fat diet-fed, ob/ob, or diabetic mice; and 35 mM postprandial as in severe uncontrolled diabetic (Jackson Laboratory mouse genome database, http:// phenome.jax.org/).…”

Section: Methodsmentioning

confidence: 99%

Impact of L-FABP and glucose on polyunsaturated fatty acid induction of PPARα-regulated β-oxidative enzymes

Petrescu

Huang

Martin

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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. Impact of L-FABP and glucose on polyunsaturated fatty acid induction of PPAR␣-regulated ␤-oxidative enzymes. Am J Physiol Gastrointest Liver Physiol 304: G241-G256, 2013. First published December 13, 2012; doi:10.1152/ajpgi.00334.2012.-Liver fatty acid binding protein (L-FABP) is the major soluble protein that binds very-long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) in hepatocytes. However, nothing is known about L-FABP's role in n-3 PUFA-mediated peroxisome proliferator activated receptor-␣ (PPAR␣) transcription of proteins involved in long-chain fatty acid (LCFA) ␤-oxidation. This issue was addressed in cultured primary hepatocytes from wild-type, L-FABP-null, and PPAR␣-null mice with these major findings: 1) PUFA-mediated increase in the expression of PPAR␣-regulated LCFA ␤-oxidative enzymes, LCFA/LCFA-CoA binding proteins (L-FABP, ACBP), and PPAR␣ itself was L-FABP dependent; 2) PPAR␣ transcription, robustly potentiated by high glucose but not maltose, a sugar not taken up, correlated with higher protein levels of these LCFA ␤-oxidative enzymes and with increased LCFA ␤-oxidation; and 3) high glucose altered the potency of n-3 relative to n-6 PUFA. This was not due to a direct effect of glucose on PPAR␣ transcriptional activity nor indirectly through de novo fatty acid synthesis from glucose. Synergism was also not due to glucose impacting other signaling pathways, since it was observed only in hepatocytes expressing both L-FABP and PPAR␣. Ablation of L-FABP or PPAR␣ as well as treatment with MK886 (PPAR␣ inhibitor) abolished/ reduced PUFA-mediated PPAR␣ transcription of these genes, especially at high glucose. Finally, the PUFA-enhanced L-FABP distribution into nuclei with high glucose augmentation of the L-FABP/ PPAR␣ interaction reveals not only the importance of L-FABP for PUFA induction of PPAR␣ target genes in fatty acid ␤-oxidation but also the significance of a high glucose enhancement effect in diabetes. polyunsaturated; fatty acid; oxidation; glucose; liver fatty acid binding protein; peroxisome proliferator activated receptor-␣; hepatocyte THE SEVERAL FORMS OF DIABETES mellitus and associated complications are the sixth leading cause of death in the US, and incidence is rising (22,101,123,132). Nearly 80% of people with diabetes die of cardiovascular disease (CVD), particularly coronary heart disease (20, 102). Thus benefits of any lipid intervention may be greatest in these individuals (97,102,114). Although dietary improvements, exercise, and statins have significantly decreased the incidence and severity of CVD, residual CVD risk remains especially high (62-82%) among individuals with diabetes mellitus, even with optimum statin therapy (102,113). This difference is thought to be due primarily to a residual dyslipidemia in this population, particularly hypertriglyceridemia (113).The liver is key in maintaining homeostasis of long-chain fatty acid (LCFA) and glucose metabolism (14, 105). Hepatic peroxisome proliferator activated receptor-␣ (PPAR␣) is the major transcription factor con...

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Section: Methodsmentioning

confidence: 99%

Impact of L-FABP and glucose on polyunsaturated fatty acid induction of PPARα-regulated β-oxidative enzymes

Petrescu

Huang

Martin

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Ten SNPs have been validated in the coding region of FABP5, 7 missense and 3 synonymous (not affecting the amino acid sequence). Two SNPs in the regulatory region of FABP5 have been identified in association with type 2 diabetes mellitus (T2DM): rs454550 showed significant association with T2DM in a non-Hispanic White sample, and a newly reported SNP at genomic position 82354416 was associated with T2DM in both non-Hispanic White and African sample populations (Bu et al, 2011). A missense 340G>C (Gly114Arg) SNP in the coding region of FABP5 has been linked to autism (Maekawa et al, 2010).…”

Section: Descriptionmentioning

confidence: 99%

“…Two single nucleotide polymorphisms in the regulatory region of FABP5 are associated with type 2 diabetes in humans (Bu et al, 2011). Human islet cells and insulin-secreting rat INS1E β-cells express FABP5 (Hyder et al, 2010).…”

Section: Diabetesmentioning

confidence: 99%

FABP5 (fatty acid binding protein 5 (psoriasis-associated))

Balcom¹,

Liu²,

Poon³

et al. 2017

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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The FABP5 gene encodes a member of the fatty acid binding protein family which is also known as epidermal or cutaneous FABP. Overexpression of FABP5 is associated with a number of cancers including breast and prostate cancers, as well as psychiatric disorders and diabetes. FABP5 can bind retinoic acid as well as polyunsaturated and saturated fatty acids. Transport of FABP5 ligands such as arachidonic acid and retinoic acid to the nucleus is believed to activate the nuclear receptor peroxisome proliferator-activated receptor beta/delta (PPARβ/δ).

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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%

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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Polymorphisms in fatty acid binding protein 5 show association with type 2 diabetes

Cited by 33 publications

References 52 publications

Impact of L-FABP and glucose on polyunsaturated fatty acid induction of PPARα-regulated β-oxidative enzymes

Impact of L-FABP and glucose on polyunsaturated fatty acid induction of PPARα-regulated β-oxidative enzymes

FABP5 (fatty acid binding protein 5 (psoriasis-associated))

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

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