Presence of fatty-acid-binding protein 4 expression in human epicardial adipose tissue in metabolic syndrome

Vural, Burçak; Atalar, Fatmahan; Çiftçi, Çavlan; Demirkan, Ayşe; Süsleyici-Duman, Belgin; Günay, Demet; Akpınar, Belhhan; Sağbaş, Ertan; Özbek, Uğur; Büyükdevrim, Ahmet Sevim

doi:10.1016/j.carpath.2008.02.006

Cited by 76 publications

(44 citation statements)

References 67 publications

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“…Previous studies reported similar levels of FABP4 mRNA in human VAT and SAT (6,44,45). Our findings that FABP4 protein is higher in both human VAT and mouse intra-abdominal fat suggest that FABP4 may also be regulated posttranscriptionally.…”

Section: Discussionsupporting

confidence: 79%

“…Visceral adipocytes are smaller and less responsive to TZD compared with subcutaneous adipocytes (41), possibly due to the reduced PPARg. Furthermore, the VAT secretes higher levels of proinflammatory cytokines (8,42,43).Previous studies reported similar levels of FABP4 mRNA in human VAT and SAT (6,44,45). Our findings that FABP4 protein is higher in both human VAT and mouse intra-abdominal fat suggest that FABP4 may also be regulated posttranscriptionally.…”

supporting

confidence: 73%

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FABP4 Attenuates PPARγ and Adipogenesis and Is Inversely Correlated With PPARγ in Adipose Tissues

et al. 2014

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Fatty acid binding protein 4 (FABP4, also known as aP2) is a cytoplasmic fatty acid chaperone expressed primarily in adipocytes and myeloid cells and implicated in the development of insulin resistance and atherosclerosis. Here we demonstrate that FABP4 triggers the ubiquitination and subsequent proteasomal degradation of peroxisome proliferator-activated receptor g (PPARg), a master regulator of adipogenesis and insulin responsiveness. Importantly, FABP4-null mouse preadipocytes as well as macrophages exhibited increased expression of PPARg, and complementation of FABP4 in the macrophages reversed the increase in FABP4 expression. The FABP4-null preadipocytes exhibited a remarkably enhanced adipogenesis compared with wild-type cells, indicating that FABP4 regulates adipogenesis by downregulating PPARg. We found that the FABP4 level was higher and PPARg level was lower in human visceral fat and mouse epididymal fat compared with their subcutaneous fat. Furthermore, FABP4 was higher in the adipose tissues of obese diabetic individuals compared with healthy ones. Suppression of PPARg by FABP4 in visceral fat may explain the reported role of FABP4 in the development of obesity-related morbidities, including insulin resistance, diabetes, and atherosclerosis. Adiposity is closely correlated with important physiological parameters such as blood pressure, systemic insulin sensitivity, dyslipidemia, and serum triglyceride levels (1,2), rendering obesity to an independent risk factor for myocardial infarction, stroke, type 2 diabetes, and certain cancers (3). Among adipose tissues, visceral fat is more closely correlated with obesity-associated pathologies than overall adiposity (4-8).The nuclear receptor peroxisome proliferatoractivated receptor g (PPARg) is a master regulator of adipose cell differentiation, playing a critical role in systemic lipid and glucose metabolism (9). PPARg is activated by natural or synthetic agonists such as the antidiabetic thiazolidinedione (TZD) (10). Activated PPARg is a master regulator of adipogenesis, acting as a transcription factor of genes expressed in mature adipocytes, including fatty acid binding protein (FABP4), CD36, lipoprotein lipase (LPL), and adiponectin, all of which contain peroxisome proliferator response elements (PPREs) (11). PPARg is also expressed in myeloid cells, and its activation promotes an anti-inflammatory phenotype (11). Disruption of PPARg specifically in myeloid cells also predisposes METABOLISMmice to the development of diet-induced obesity, insulin resistance, and glucose intolerance (12), whereas activation of PPARg within macrophages promotes lipid efflux, thereby stabilizing atherosclerotic lesions (13). A major target gene of PPARg is the lipid transporter FABP4, also known as aP2 (14). PPARg induces FABP4 almost exclusively in adipocytes and macrophages. FABP4 acts as a fatty acids chaperone, which couples intracellular lipids to biological targets and signaling pathways (15,16). FABP4 has been implicated in several aspects of the metabolic syndro...

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Section: Discussionsupporting

confidence: 79%

supporting

confidence: 73%

FABP4 Attenuates PPARγ and Adipogenesis and Is Inversely Correlated With PPARγ in Adipose Tissues

et al. 2014

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“…Nevertheless, additional reports have suggested that FABP4 may also promote heart dysfunction through its direct action on cardiomyocytes. Increased FABP4 expression has been reported in human epicardial adipose tissue from metabolic syndrome patients (Vural et al 2008), suggesting a paracrine effect on cardiac cells. Additionally, a recent study by Furuhashi and coworkers showed that FABP4 that is locally produced by epicardial/ perivascular fat and macrophages contributes to the development of coronary atherosclerosis (Furuhashi et al 2016), highlighting the potential paracrine role of this adipokine.…”

Section: Fabp4 Cardiac Dysfunction and Hfmentioning

confidence: 96%

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

Rodríguez-Calvo¹,

Girona²,

Alegret

et al. 2017

Journal of Endocrinology

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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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“…This can be explained by two main mechanisms: the antilipolytic effect of insulin, which is lower in VAT, and the increased number of β adrenergic receptors at this level, especially β3, the stimulation of which activates lipolysis. It has been recently discovered that the fatty acid-binding protein 4 (FABP4/aP2) present in adipocytes and macrophages in atherosclerotic lesions is also expressed in EAT and is elevated in patients with metabolic syndrome [33].…”

Section: Biochemical Characteristics Of Eatmentioning

confidence: 99%

“…Some features of EAT differentiate it from SAT: the small size of adipocytes; the content of certain fatty free acids and the high content of proteins; the high rate of incorporation of FFA in the EAT; the FFA synthesis, as well as the FFA degradation and insulin-sensitive lipogenesis; the low rate of glucose usage; and the low lipoprotein-lipase, stearol-CoA desaturase, and acetyl CoA alpha-carboxylase mRNA expression [33,34].…”

Section: Biochemical Characteristics Of Eatmentioning

confidence: 99%

Epicardial adipose tissue and relationship with coronary artery disease

et al. 2011

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AbstractEpicardial adipose tissue (EAT) is metabolically active tissue that accumulates around the coronary arteries. Epicardial fat is a rich source of free fatty acids and may contribute to local inflammatory load by increased synthesis of inflammatory cytokines. Direct passage of bioactive molecules into the coronary arteries due to close contact with the vascular wall and the lack of fascia may contribute to the pathogenesis of coronary artery disease. Direct correlation between visceral fat and EAT defines the latter as an indirect marker of intra-abdominal visceral adiposity. EAT is related to anthropometric and clinical features of the metabolic syndrome (MS) and to hepatic transaminases as markers of steatohepatitis. An increase in EAT thickness is related to an increase in left ventricular mass and is correlated with atrial enlargement and impairment in diastolic filling in obesity. Echocardiographic study of EAT is an easy and reliable imaging indicator of visceral adiposity and cardiovascular risk. EAT is an independent factor strongly correlated with significant coronary stenosis. A level of EAT above an established average value can be considered a predictive marker of cardiovascular risk. We review the most recent studies proving the specific active role of EAT in the development of cardiac disease.

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Presence of fatty-acid-binding protein 4 expression in human epicardial adipose tissue in metabolic syndrome

Cited by 76 publications

References 67 publications

FABP4 Attenuates PPARγ and Adipogenesis and Is Inversely Correlated With PPARγ in Adipose Tissues

FABP4 Attenuates PPARγ and Adipogenesis and Is Inversely Correlated With PPARγ in Adipose Tissues

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

Epicardial adipose tissue and relationship with coronary artery disease

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