Physiological properties and functions of intracellular fatty acid-binding proteins

Coe, Natalie Ribarik; Bernlohr, David A.

doi:10.1016/s0005-2760(97)00205-1

Cited by 301 publications

(260 citation statements)

References 167 publications

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“…AFABP serves as a lipid-binding chaperone for longchain NEFA [15]. Structure-function studies show that AFABP consists of a beta barrel formed by ten antiparallel beta strands defining an interior water-filled binding cavity that is used as the NEFA-binding site [16,17].…”

Section: Production and Structure Of Afabpmentioning

confidence: 99%

Adipocyte fatty acid binding protein: a novel adipokine involved in the pathogenesis of metabolic and vascular disease?

2012

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Adipocyte fatty acid binding protein (AFABP, also known as aP2 and FABP4) has recently been introduced as a novel fat-derived circulating protein. AFABP serum concentrations are positively correlated with markers of the metabolic syndrome and vascular disease in various cross-sectional and interventional studies. Furthermore, a small set of prospective studies indicates that high AFABP serum levels at baseline predict the risk for metabolic and vascular morbidity and mortality. Studies in Afabp (also known as Fabp4) knockout mice and AFABP inhibitortreated animals suggest that total AFABP promotes insulin resistance, hypertriacylglycerolaemia and atherosclerosis by ligand/ligand delivery, as well as ligand-independent mechanisms. In contrast, the pathophysiological significance of circulating AFABP and the mechanisms leading to its release remain to be established. The current review summarises recent findings on the regulation and potential role of AFABP in metabolic and vascular disease.

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Section: Production and Structure Of Afabpmentioning

confidence: 99%

Adipocyte fatty acid binding protein: a novel adipokine involved in the pathogenesis of metabolic and vascular disease?

2012

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“…Fatty acid‐binding protein 4 (FABP4), also known as aP2, is a member of the intracellular FABP family that bind long‐chain fatty acids and other hydrophobic ligands26, 27 and is involved in fatty acid uptake, transport, and metabolism 28, 29. Interestingly, in the livestock field, it is known as a key candidate gene for meat marbling, which is a phenomenon quite similar to muscle fatty infiltration 30, 31.…”

Section: Introductionmentioning

confidence: 99%

Fatty acid‐binding protein 4 regulates fatty infiltration after rotator cuff tear by hypoxia‐inducible factor 1 in mice

Lee

Kim

et al. 2017

J cachexia sarcopenia muscle

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BackgroundFatty infiltration in skeletal muscle is directly linked to loss of muscle strength and is associated with various adverse physical outcomes such as muscle atrophy, inflammation, insulin resistance, mobility impairments, and even mortality in the elderly. Aging, mechanical unloading, muscle injury, and hormonal imbalance are main causes of muscle fat accumulation, and the fat cells are derived from muscle stem cells via adipogenic differentiation. However, the pathogenesis and molecular mechanisms of fatty infiltration in muscles are still not fully defined. Fatty acid‐binding protein 4 (FABP4) is a carrier protein for fatty acids and is involved in fatty acid uptake, transport, and lipid metabolism. Rotator cuff tear (RCT) usually occurs in the elderly and is closely related with fatty infiltration in injured muscle. To investigate potential mechanisms for fatty infiltration other than adipogenic differentiation of muscle stem cells, we examined the role of FABP4 in muscle fatty infiltration in an RCT mouse model.MethodsIn the RCT model, we evaluated the expression of FABP4 by qRT‐PCR, western blotting, and immunohistochemical analyses. Histological changes such as inflammation and fat accumulation in the injured muscles were examined immunohistochemically. To evaluate whether hypoxia induces FABP4 expression, the levels of FABP4 mRNA and protein in C3H10T1/2 cells after hypoxia were examined. Using a transient transfection assay in 293T cells, we assessed the promoter activity of FABP4 by hypoxia‐inducible factors (HIFs). Additionally, we evaluated the reduction in FABP4 expression and fat accumulation using specific inhibitors for HIF1 and FABP4, respectively.ResultsFABP4 expression was significantly increased after RCT in mice, and its expression was localized in the intramuscular fatty region. Rotator cuff tear‐induced FABP4 expression was up‐regulated by hypoxia. HIF1α, which is activated by hypoxia, augmented the promoter activity of FABP4, together with HIF1β. Hypoxia‐induced FABP4 expression was significantly decreased by HIF1 inhibitor treatment. Furthermore, in RCT model mice, fat accumulation was remarkably reduced by FABP4 inhibitor treatment.ConclusionsThis study shows that RCT induces FABP4 expression, leading to fat accumulation in injured muscle. FABP4 transcription is regulated by the direct binding of HIF1 to the FABP4 promoter in the hypoxic condition induced by RCT. Fat accumulation in injured muscle was reduced by the inhibition of FABP4. Ultimately, in the RCT model, we identified a novel mechanism for fatty infiltration by FABP4, which differs from adipogenic differentiation of muscle stem cells, and we found that fatty infiltration might be regulated by inhibition of HIF1 or FABP4.

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“…Since LCPUFAs are insoluble in an aqueous cellular environment, fatty acid binding proteins (FABPs) are essential to function as cellular shuttles to transport LCPUFAs to appropriate intracellular compartments (Coe and Bernlohr, 1998). Small 14 -15 kDa cytoplasmic FABPs belong to a family consisting of at least 13 different widely distributed proteins (Banaszak et al, 1994;Veerkamp and Maatman, 1995;Glatz and van der Vusse, 1996).…”

Section: Introductionmentioning

confidence: 99%

Heart-Type Fatty Acid Binding Protein Regulates Dopamine D₂Receptor Function in Mouse Brain

Shioda¹,

Yamamoto²,

Watanabe³

et al. 2010

J. Neurosci.

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Physiological properties and functions of intracellular fatty acid-binding proteins

Cited by 301 publications

References 167 publications

Adipocyte fatty acid binding protein: a novel adipokine involved in the pathogenesis of metabolic and vascular disease?

Adipocyte fatty acid binding protein: a novel adipokine involved in the pathogenesis of metabolic and vascular disease?

Fatty acid‐binding protein 4 regulates fatty infiltration after rotator cuff tear by hypoxia‐inducible factor 1 in mice

Heart-Type Fatty Acid Binding Protein Regulates Dopamine D₂Receptor Function in Mouse Brain

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Physiological properties and functions of intracellular fatty acid-binding proteins

Cited by 301 publications

References 167 publications

Adipocyte fatty acid binding protein: a novel adipokine involved in the pathogenesis of metabolic and vascular disease?

Adipocyte fatty acid binding protein: a novel adipokine involved in the pathogenesis of metabolic and vascular disease?

Fatty acid‐binding protein 4 regulates fatty infiltration after rotator cuff tear by hypoxia‐inducible factor 1 in mice

Heart-Type Fatty Acid Binding Protein Regulates Dopamine D2Receptor Function in Mouse Brain

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Heart-Type Fatty Acid Binding Protein Regulates Dopamine D₂Receptor Function in Mouse Brain