Circulating Levels of Fatty Acid-Binding Protein Family and Metabolic Phenotype in the General Population

Ishimura, Shutaro; Furuhashi, Masato; Watanabe, Yuki; Hoshina, Kyoko; Fuseya, Takahiro; Mita, Tomohiro; Okazaki, Yusuke; Koyama, Masayuki; Tanaka, Marenao; Akasaka, Hiroshi; Ohnishi, Hirofumi; Yoshida, Hiroyuki; Saitoh, Shigeyuki; Miura, Tetsuji

doi:10.1371/journal.pone.0081318

Cited by 131 publications

(151 citation statements)

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“…For example, intrarenal CD36 has been identified as a novel mediator in renal diseases associated with proteinuria and renal dysfunction (35). The elevated level of serum/plasma/urinary Fabp4 is considered a predictor or biomarker for renal dysfunction in diabetes and cardiovascular diseases (23)(24)(25)(26)(27). Hence, we further hypothesized that these affected IUGR offspring fed with HFD would develop metabolic perturbations and kidney injury in adulthood that might be associated with alterations of both renal CD36 and Fabp4 gene expression.…”

Section: Articlesmentioning

confidence: 99%

“…Emerging evidence suggested that CD36 (19)(20)(21)(22) and Fabp4 (23)(24)(25)(26)(27) are highly implicated in the pathogenesis of HFDinduced cell damage. For example, intrarenal CD36 has been identified as a novel mediator in renal diseases associated with proteinuria and renal dysfunction (35).…”

Section: Articlesmentioning

confidence: 99%

“…CD36 (19)(20)(21)(22) and fatty acid-binding protein 4 (Fabp4) (23)(24)(25)(26)(27) may mediate chronic inflammation, insulin resistance, oxidant stress, and fibrosis involved in proatherogenic hyperlipidemic states such as obesity. In this study, we followed these affected IUGR offspring from 4 to 20 wk of age and compared the metabolic impacts of post-weaning diet (HFD vs. normal diet (ND)) on handling of lipoproteins, hypertension, and renal function.…”

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confidence: 99%

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Post-weaning high-fat diet accelerates kidney injury, but not hypertension programmed by maternal diabetes

et al. 2015

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Background:The aim of this study was to establish the underlying mechanisms by which a post-weaning high-fat diet (HFD) accelerates the perinatal programming of kidney injury occurring in the offspring of diabetic mothers. Methods: Male mice, offspring of nondiabetic and diabetic dams were fed with normal diet (ND) or HFD from 4 to 20 wk of age. Rat renal proximal tubular cells were used in vitro. results: On ND, the offspring of dams with severe maternal diabetes had an intrauterine growth restriction (IUGR) phenotype and developed mild hypertension and evidence of kidney injury in adulthood. Exposing the IUGR offspring to HFD resulted in rapid weight gain, catch-up growth, and later to profound kidney injury with activation of renal TGFβ1 and collagen type IV expression, increased oxidative stress, and enhanced renal lipid deposition, but not systemic hypertension. Given our data, we speculate that HFD or free fatty acids may accelerate the process of perinatal programming of kidney injury, via increased CD36 and fatty acid-binding protein 4 expression, which may target reactive oxygen species, nuclear factor-kappa B, and TGFβ1 signaling in vivo and in vitro. conclusion: Early postnatal exposure to overnutrition with a HFD increases the risk of development of kidney injury, but not hypertension, in IUGR offspring of dams with maternal diabetes.d iabetes during pregnancy, whether gestational or pregestational diabetes (type 1 or type 2), results in offspring at high risk of developing hypertension, cardiovascular disease, and chronic kidney disease in adult life. This phenomenon, termed perinatal programming, in which intrauterine events are associated with later adverse changes, has attracted much attention (1-3). Substantial epidemiologic data have also suggested that the offspring whose mothers were diabetic during pregnancy are susceptible to metabolic disturbances induced by postnatal overnutrition, as seen with high-fat diet (HFD) or with increased caloric intake in early life (1)(2)(3)(4).Women who have diabetes during pregnancy and/or are obese and hyperinsulinemic are at risk of delivering macrosomic newborns (high birth weight), and both shortand long-term outcomes of macrosomic neonates are influenced by postnatal overnutrition (1-4). In high-birth-weight neonates, subsequent growth in infancy and risk of becoming obese or diabetic are directly and linearly linked-e.g., the higher the birth weight, the greater the risk of overweight and metabolic disturbances later in life (1-4). In contrast, pregnant women with severe, uncontrolled diabetes or diabetic complications, such as diabetic nephropathy and/or retinopathy, are at high risk of having a microsomic fetus (i.e., a fetus with intrauterine growth restriction (IUGR)) (5,6). Such infants may be markedly small for dates; but many develop excessive weight gain and increased fat deposition in early infancy, a proxy for neonatal overnutrition (7,8). However, the long-term outcome of IUGR offspring who experience overnutrition in early life is incomplet...

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Section: Articlesmentioning

confidence: 99%

Section: Articlesmentioning

confidence: 99%

mentioning

confidence: 99%

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Post-weaning high-fat diet accelerates kidney injury, but not hypertension programmed by maternal diabetes

et al. 2015

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“…A full colour version of this figure is available at http:// dx.doi.org/10.1530/JOE-17-0031. correlated with adiposity (Xu et al 2006, Ishimura et al 2013. Despite its lack of an N-terminal secretory signal sequence (Furuhashi & Hotamisligil 2008), FABP4 has been reported to be released from adipocytes through additional mechanisms (Coe et al 1999, Scheja et al 1999, Shen et al 1999, Mita et al 2015 and acts as an adipokine in several organs, including the heart (Fig.…”

Section: Figurementioning

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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“…It is possible that the level of FABP4 secreted from endothelial cells is sufficient for causing significant effects on nearby vascular endothelial cells and smooth muscle cells, leading to an inflammatory response, proliferation, and migration from the media into the intima. The circulating level of FABP4 is ≈20 ng/mL (1 nmol/L) in humans 19. Since autocrine and paracrine actions of the secreted FABP4 derived from regenerated endothelial cells were focused on in the present study, the concentration of recombinant FABP4 used (≈200 nmol/L) seems to be reasonable and physiological in the local area.…”

Section: Discussionmentioning

confidence: 81%

Ectopic Fatty Acid–Binding Protein 4 Expression in the Vascular Endothelium is Involved in Neointima Formation After Vascular Injury

Fuseya

Furuhashi

Matsumoto

et al. 2017

JAHA

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BackgroundFatty acid‐binding protein 4 (FABP4) is expressed in adipocytes, macrophages, and endothelial cells of capillaries but not arteries. FABP4 is secreted from adipocytes in association with lipolysis, and an elevated circulating FABP4 level is associated with obesity, insulin resistance, and atherosclerosis. However, little is known about the link between FABP4 and endovascular injury. We investigated the involvement of ectopic FABP4 expression in endothelial cells in neointima hyperplasia after vascular injury.Methods and ResultsFemoral arteries of 8‐week‐old male mice were subjected to wire‐induced vascular injury. After 4 weeks, immunofluorescence staining showed that FABP4 was ectopically expressed in endothelial cells of the hyperplastic neointima. Neointima formation determined by intima area and intima to media ratio was significantly decreased in FABP4‐defficient mice compared with that in wild‐type mice. Adenovirus‐mediated overexpression of FABP4 in human coronary artery endothelial cells (HCAECs) in vitro increased inflammatory cytokines and decreased phosphorylation of nitric oxide synthase 3. Furthermore, FABP4 was secreted from HCAECs. Treatment of human coronary smooth muscle cells or HCAECs with the conditioned medium of Fabp4‐overexpressed HCAECs or recombinant FABP4 significantly increased gene expression of inflammatory cytokines and proliferation‐ and adhesion‐related molecules in cells, promoted cell proliferation and migration of human coronary smooth muscle cells, and decreased phosphorylation of nitric oxide synthase 3 in HCAECs, which were attenuated in the presence of an anti‐FABP4 antibody.ConclusionsEctopic expression and secretion of FABP4 in vascular endothelial cells contribute to neointima formation after vascular injury. Suppression of ectopic FABP4 in the vascular endothelium would be a novel strategy against post‐angioplasty vascular restenosis.

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Circulating Levels of Fatty Acid-Binding Protein Family and Metabolic Phenotype in the General Population

Cited by 131 publications

References 40 publications

Post-weaning high-fat diet accelerates kidney injury, but not hypertension programmed by maternal diabetes

Post-weaning high-fat diet accelerates kidney injury, but not hypertension programmed by maternal diabetes

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

Ectopic Fatty Acid–Binding Protein 4 Expression in the Vascular Endothelium is Involved in Neointima Formation After Vascular Injury

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