FABP 4 is associated with inflammatory markers and metabolic syndrome in morbidly obese women

Terra, Ximena; Quintero, Yunuen; Auguet, Teresa; Porras, José Antonio; Hernández, Mercè; Sabench, Fàtima; Aguilar, Carmen; Luna, Anna; Déjardin, Daniel del Castillo; Richart, C

doi:10.1530/eje-10-1195

Cited by 116 publications

(84 citation statements)

References 34 publications

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“…Until recently, the biological functions of aP2 in the pathogenesis of chronic diseases have been attributed exclusively to its intracellular action. However, newer studies have demonstrated that aP2 is released from adipocytes; its levels are signifi cantly increased in experimental and human obesity and strongly correlate with cardiometabolic diseases in numerous human studies (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). We have also shown that the secreted form of aP2 is a bona fi de adipokine that regulates systemic metabolism, and that antibody-mediated neutralization exhibits potent antidiabetic activity in preclinical models ( 15 ).…”

Section: A Nonclassical Vesicular Pathway Mediates Ap2 Secretion Uponmentioning

confidence: 80%

“…These studies also demonstrated that circulating aP2 levels are signifi cantly increased in dietary and genetic models of obesity, and that neutralizing circulating aP2 with a polyclonal antibody improved metabolic parameters and diabetes in mice ( 15 ). A growing body of association studies in humans also shows that circulating aP2 levels are positively correlated with obesity, metabolic pathologies, and cardiovascular disease (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). In addition, recent studies have revealed multiple other potential roles for extracellular aP2 ( 27,28 ).…”

Section: Cell Culturementioning

confidence: 95%

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Secretion of fatty acid binding protein aP2 from adipocytes through a nonclassical pathway in response to adipocyte lipase activity

Ertunc

Sikkeland

Fenaroli

et al. 2015

Journal of Lipid Research

125

172

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Journal of Lipid Research Volume 56, 2015 423Adipose tissue is an endocrine organ whose products orchestrate the metabolic functions of various tissues, including brain, pancreas, and liver, to maintain systemic homeostasis. Adipocytes respond to metabolic and immune cues by mobilizing their fat stores through lipolysis and by secreting a variety of hormones and cytokines ( 1, 2 ). Such signals converge on target tissues, for example on liver to regulate glucose production, and on ␤ cells to modulate insulin production. A critical molecule for the integration of adipocyte biology with systemic metabolic regulation is aP2 [fatty acid binding protein (FABP) 4], a lipid binding protein that is upregulated during differentiation of adipocytes and upon macrophage activation ( 3, 4 ). Since its identifi cation, aP2 has been studied primarily for its intracellular functions in lipid metabolism and infl ammation ( 3,4 ). Genetic deletion models demonstrated that this FABP plays a critical role in the pathogenesis of several chronic metabolic diseases, including diabetes, atherosclerosis, and fatty liver. Mice defi cient in aP2 or aP2 and the related protein FABP5/mal1 together have improved adipose and liver function, increased insulin sensitivity, and reduced fatty liver and cardiovascular disease in the context of high-fat diet and genetic mouse models of obesity and atherosclerosis ( 5-12 ). The link between aP2 and metabolic disease is also supported by genetic association studies in multiple populations demonstrating metabolic and cardiovascular benefi ts in individuals carrying a rare haploinsuffi ciency mutation in the aP2 locus, validating the relevance of this pathway in human disease ( 13,14 ).

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Section: A Nonclassical Vesicular Pathway Mediates Ap2 Secretion Uponmentioning

confidence: 80%

Section: Cell Culturementioning

confidence: 95%

Secretion of fatty acid binding protein aP2 from adipocytes through a nonclassical pathway in response to adipocyte lipase activity

Ertunc

Sikkeland

Fenaroli

et al. 2015

Journal of Lipid Research

125

172

View full text Add to dashboard Cite

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“…Cash et al (39) first suggested that DNA hypomethylation is involved in the development of cardiovascular disease, and evidence from animal studies has suggested that global DNA hypomethylation is associated with atherosclerotic lesions. A number of previous reports have focused on alterations in the DNA methylation of specific genes associated with AS (40,41). Global hypomethylation affects CpG dinucleotides in repetitive elements and in certain gene-specific promoter CpG islands (42).…”

Section: Discussionmentioning

confidence: 99%

Ratio of S-adenosylmethionine to S-adenosylhomocysteine as a sensitive indicator of atherosclerosis

Zhang

Liu

et al. 2016

Mol Med Report

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Abstract. The present study aimed to confirm whether the ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH) is a sensitive indicator, and whether it can be used as a biomarker for the clinical diagnosis of atherosclerosis. Apolipoprotein E (ApoE) -/-mice were randomly divided into four groups and fed with a high methionine diet for 15 weeks. Serum levels of homocysteine (Hcy) were measured using an automatic biochemistry analyzer. The concentrations of SAM and SAH were determined using high-performance liquid chromatography. The methylation levels of B1 repetitive elements, adipocyte fatty acid binding protein (FABP4), monocyte chemoattractant protein-1 (MCP-1) and extracellular superoxide dismutase (EC-SOD) were analyzed using nested touchdown-methylation-specific-polymerase chain reaction analysis. After 15 weeks, compared with the normal control group, serum concentrations of Hcy were significantly increased by 1.15-, 2.54-and 1.17-fold (P<0.05) in the ApoE -/-control group, Meth group and Meth-F group, respectively. The sizes of the atherosclerotic lesions were increased in the ApoE -/-control group, Meth group and Meth-F group, by up to 1.44-, 2.40-and 1.45-fold, respectively, compared with the normal control group (P<0.05). The concentrations of SAM were significantly increased by 3.02-, 3.42-and 2.46-fold in the ApoE -/-control group, Meth group and Meth-F group, respectively (P<0.05). The ratios of SAM/SAH were increased by 1.67-and 2.75-fold in the in ApoE -/-control group and Meth group, respectively, compared with the normal control group. The methylation levels of B1 repetitive elements, FABP4, MCP-1 and EC-SOD were decreased and exhibited hypomethylation. The methylation statuses of these genes were correlated with the ratio of the serum levels of SAM and SAH. These findings suggested that the SAM/SAH ratio is a biomarker and may provide a sensitive indicator for the clinical diagnosis of atherosclerosis.

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“…Increasing serum aFABP levels are closely associated with impaired glucose metabolism and may also be considered a useful indicator of the development of type 2 diabetes 13 . Increasing aFABP levels have been shown to be associated with inflammatory markers such as CRP and interleukin-6 in obese individuals and those with metabolic syndrome 14 . The association of AFABP and CRP with metabolic syndrome is often explained by the association with obesity.…”

Section: Discussionmentioning

confidence: 99%

Adipocyte Fatty Acid Binding Protein and C-Reactive Protein Levels as Indicators of Insulin Resistance Development

Horáková

Pastucha²,

Stejskal³

et al. 2011

BIOMED PAP

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Background. Adipocyte fatty acid-binding protein (aFABP) has recently been identified as a potential circulating marker for metabolic syndrome. C-reactive protein (CRP), a sensitive marker of inflammation, is increased in individuals with diabetes and metabolic syndrome due to the development of subclinical inflammation. The study uses logistic regression models to analyze the relations between aFABP and CRP along with other parameters of insulin resistance. The objective was to investigate the potential use of aFABP and CRP levels as tools in the diagnosis of the metabolic syndrome.Methods and results. The following groups were studied: healthy individuals (A, n=122), obese ind1ividuals (B, n=213) and patients diagnosed with metabolic syndrome (C, n=79). Obese persons in Group B had parameters suggestive of early insulin resistance: hypertension, hyperglycaemia, QUICKI (0.305) and higher aFABP levels as compared with the healthy subjects. Group C individuals were diagnosed with metabolic syndrome, as evidenced by the QUICKI markers for insulin resistance (0.293), high aFABP levels (35.3 mg/l). CRP concentrations were lowest in Group A healthy individuals (0.67 mg/l), higher in Group B obese subjects (2.65 mg/l) and highest in Group C patients with metabolic syndrome (3.62 mg/l). Logistic regression models showed an association of aFABP and CRP with BMI (OR 1.12 and 1.39, compared Group A vs C). An association of aFABP and CRP with the QUICKI index showed OR 1.48 and 1.37 (Group A vs C); with triglyceride levels showed OR 1.68 and 1.52 (Group A vs C). An association of aFABP and CRP with glycaemia showed OR 1.48 and 1.51 (Group A vs C), with insulinaemia showed OR 1.44 and 1.38 (Group A vs C) respectively.Conclusions. AFABP levels were higher in obese individuals and highest in those with metabolic syndrome. CRP concentrations were increased in obese persons whereas individuals with metabolic syndrome were found to have high-risk CRP levels. Logistic regression models showed an association of aFABP and CRP with BMI as well as an association of aFABP and CRP with parameters of insulin resistance, namely the QUICKI index, triglyceride levels, glycaemia and insulinaemia. Both methods are of diagnostic benefit for predicting metabolic syndrome, especially in previously untreated patients.

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FABP 4 is associated with inflammatory markers and metabolic syndrome in morbidly obese women

Cited by 116 publications

References 34 publications

Secretion of fatty acid binding protein aP2 from adipocytes through a nonclassical pathway in response to adipocyte lipase activity

Secretion of fatty acid binding protein aP2 from adipocytes through a nonclassical pathway in response to adipocyte lipase activity

Ratio of S-adenosylmethionine to S-adenosylhomocysteine as a sensitive indicator of atherosclerosis

Adipocyte Fatty Acid Binding Protein and C-Reactive Protein Levels as Indicators of Insulin Resistance Development

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