Adipocyte Fatty Acid-binding Protein Modulates Inflammatory Responses in Macrophages through a Positive Feedback Loop Involving c-Jun NH2-terminal Kinases and Activator Protein-1

Hui, Xiaoyan; Li, Huiying; Zhou, Zhiguang; Lam, Karen S.L.; Xiao, Yang; Wu, Donghai; Ding, Ke; Wang, Yudong; Vanhoutte, Paul M.; Xu, Aimin

doi:10.1074/jbc.m109.097907

Cited by 150 publications

(148 citation statements)

References 48 publications

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“…Similar to adipocytes, FABP4 expression is also induced during differentiation from monocytes to macrophages, and its expression in these cells is regulated by a wide range of proinflammatory stimuli (Pelton et al 1999, Fu et al 2000, Makowski et al 2001, Fu et al 2002, Kazemi et al 2005. In macrophages, FABP4 increases the accumulation of cholesterol ester and induces foam cell formation as well as inflammatory responses through the activation of the IKK-NF-κB and JNK-AP-1 pathways (Makowski et al 2005, Hui et al 2010). FABP4 expression is controlled at the transcriptional level by CEBP (CCAAT/enhancer-binding protein) (Christy et al 1989) and PPARγ (peroxisome proliferator-activated receptor γ) (Kletzien et al 1992, Cabre et al 2007.…”

Section: Fatty Acid-binding Proteinmentioning

confidence: 99%

Role of the fatty acid-binding protein 4 in heart failure and cardiovascular disease

Rodríguez-Calvo¹,

Girona²,

Alegret

et al. 2017

Journal of Endocrinology

100

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Obesity and ectopic fat accumulation in non-adipose tissues are major contributors to heart failure (HF) and cardiovascular disease (CVD). Adipocytes act as endocrine organs by releasing a large number of bioactive molecules into the bloodstream, which participate in a communication network between white adipose tissue and other organs, including the heart. Among these molecules, fatty acid-binding protein 4 (FABP4) has recently been shown to increase cardiometabolic risk. Both clinical and experimental evidence have identified FABP4 as a relevant player in atherosclerosis and coronary artery disease, and it has been directly related to cardiac alterations such as left ventricular hypertrophy (LVH) and both systolic and diastolic cardiac dysfunction. The available interventional studies preclude the establishment of a direct causal role of this molecule in CVD and HF and propose FABP4 as a biomarker rather than as an aetiological factor. However, several experimental reports have suggested that FABP4 may act as a direct contributor to cardiac metabolism and physiopathology, and the pharmacological targeting of FABP4 may restore some of the metabolic alterations that are conducive to CVD and HF. Here, we review the current knowledge regarding FABP4 in the context of HF and CVD as well as the molecular basis by which this protein participates in the regulation of cardiac function.

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Section: Fatty Acid-binding Proteinmentioning

confidence: 99%

Role of the fatty acid-binding protein 4 in heart failure and cardiovascular disease

Rodríguez-Calvo¹,

Girona²,

Alegret

et al. 2017

Journal of Endocrinology

100

View full text Add to dashboard Cite

show abstract

“…Lipopolysaccharides (LPS) are potent TLR4 agonists that induce AFABP production in macrophages [47]. LPS stimulates AFABP transcription through Jun N-terminal kinase (JNK), which in turn induces c-Jun recruitment to a highly conserved activator protein-1 recognition site within the proximal region of the AFABP promoter [49]. In addition, LPS-induced JNK phosphorylation, activator protein-1 stimulation and production of proinflammatory cytokines are significantly attenuated by pharmacological or genetic AFABP suppression in macrophages [49].…”

Section: The Role Of Afabp In the Pathogenesis Of Atherosclerosismentioning

confidence: 99%

“…LPS stimulates AFABP transcription through Jun N-terminal kinase (JNK), which in turn induces c-Jun recruitment to a highly conserved activator protein-1 recognition site within the proximal region of the AFABP promoter [49]. In addition, LPS-induced JNK phosphorylation, activator protein-1 stimulation and production of proinflammatory cytokines are significantly attenuated by pharmacological or genetic AFABP suppression in macrophages [49]. Besides TLR4-agonistic LPS, the TLR2 ligand zymosan and the TLR3 ligand polyinosine:polycytidylic acid significantly upregulate AFABP in murine macrophages [47].…”

Section: The Role Of Afabp In the Pathogenesis Of Atherosclerosismentioning

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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“…Recently, it was demonstrated that macrophage inflammatory responses leading to cytokine production via JNK (c-Jun N-terminal kinase) and AP1 (activator protein-1) require AFABP, the transcription of which is in turn mediated by JNK (15). AFABP has also been shown to be necessary for macrophage endoplasmic reticulum (ER) stress response to inflammatory signals (5).…”

Section: Tissue-specific Fabp Functionsmentioning

confidence: 99%

Tissue-specific Functions in the Fatty Acid-binding Protein Family

Storch

Thumser

2010

Journal of Biological Chemistry

297

215

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Adipocyte Fatty Acid-binding Protein Modulates Inflammatory Responses in Macrophages through a Positive Feedback Loop Involving c-Jun NH2-terminal Kinases and Activator Protein-1

Cited by 150 publications

References 48 publications

Role of the fatty acid-binding protein 4 in heart failure and cardiovascular disease

Role of the fatty acid-binding protein 4 in heart failure and cardiovascular disease

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

Tissue-specific Functions in the Fatty Acid-binding Protein Family

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