Adipocyte Fetuin-A Contributes to Macrophage Migration into Adipose Tissue and Polarization of Macrophages

Chatterjee, Priyajit; Seal, Soma; Mukherjee, Sandip; Kundu, Rakesh; Mukherjee, Sutapa; Ray, Sukanta; Mukhopadhyay, Satinath; Majumdar, Subeer S.; Bhattacharya, Samir

doi:10.1074/jbc.c113.495473

Cited by 112 publications

(89 citation statements)

References 24 publications

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“…We also reported an increase in fetuin-A mRNA and protein in obese mice. In addition, Chatterjee et al have reported an increase in adipose tissue fetuin-A in visceral adipose tissue of obese diabetic individuals (n=5) and mice [3]. Thus, based on these recent publications, in addition to being a hepatokine, fetuin-A needs to be considered as an adipokine, since fetuin-A mRNA and protein are present in adipose tissue [2,3], and fetuin-A contributes to insulin resistance.…”

Section: Tlr4 Toll-like Receptormentioning

confidence: 99%

Plasma fetuin-A does not correlate with monocyte TLR4 in humans

2015

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Section: Tlr4 Toll-like Receptormentioning

confidence: 99%

Plasma fetuin-A does not correlate with monocyte TLR4 in humans

2015

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“…Besides its inhibitory effect on insulin receptors, fetuin-A, together with NEFA, induces inflammation in visceral adipocytes in a TLR4-dependent manner [28][29][30]. Recent evidence suggests that fetuin-A triggers M1 polarisation of adipose tissue macrophages [31]. However, fetuin-A, an abundant fetal serum protein, has multiple roles.…”

Section: Introductionmentioning

confidence: 99%

Metabolic crosstalk between fatty pancreas and fatty liver: effects on local inflammation and insulin secretion

et al. 2017

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Aims/hypothesis Obesity-linked ectopic fat accumulation is associated with the development of type 2 diabetes. Whether pancreatic and liver steatosis impairs insulin secretion is controversial. We examined the crosstalk of human pancreatic fat cells with islets and the role of diabetogenic factors, i.e. palmitate and fetuin-A, a hepatokine released from fatty liver. Methods Human pancreatic resections were immunohistochemically stained for insulin, glucagon, somatostatin and the macrophage/monocyte marker CD68. Pancreatic adipocytes were identified by Oil Red O and adiponectin staining.Primary pancreatic pre-adipocytes and differentiated adipocytes were co-cultured with human islets isolated from organ donors and the metabolic crosstalk between fatty liver and fatty pancreas was mimicked by the addition of palmitate and fetuin-A. Insulin secretion was evaluated by ELISA and RIA. Cytokine expression and secretion were assessed by RT-PCR and multiplex assay, respectively. Subcellular distribution of proteins was examined by confocal microscopy and protein phosphorylation by western blotting. Results In human pancreatic parenchyma, highly differentiated adipocytes were detected in the proximity of islets with normal architecture and hormone distribution. Infiltration of adipocytes was associated with an increased number of CD68-positive cells within islets. In isolated primary pancreatic preadipocytes and differentiated adipocytes, palmitate and fetuin-A induced IL6, CXCL8 and CCL2 mRNA expression. Cytokine production was toll-like receptor 4 (TLR4)-dependent and further accentuated in pre-adipocytes when cocultured with islets. In islets, IL6 and CXCL8 mRNA levels were also increased by fetuin-A and palmitate. Only in macrophages within the isolated islets, palmitate and fetuin-A stimulated the production of the cytotoxic cytokine IL-1β. Palmitate, but not fetuin-A, exerted pro-apoptotic effects in islet cells. Instead, fetuin-A impaired glucose-induced insulin secretion in a TLR4-independent, but c-Jun N-terminal kinase-and Ca 2+ -dependent, manner. Conclusions/interpretation These results provide the first evidence that fetuin-A-mediated metabolic crosstalk of fatty liver with islets may contribute to obesity-linked glucose blindness of beta cells, while fatty pancreas may exacerbate local inflammation.

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“…The greatest advance was made in 2012 when Pal et al (54) reported that fetuin-A, an inflammatory glycoprotein produced by the liver and adipose tissue (55), could act as a bridge linking FFA with TLR4, leading to its activation. Clinical studies have provided further evidence for the role of fetuin-A as a mediator of FFA-induced metabolic inflammation (56,57,58).…”

Section: Toll-like Receptormentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Metabolic and inflammatory pathways on the pathogenesis of type 2 diabetes

Coope

Torsoni

Velloso

2016

European Journal of Endocrinology

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Obesity is the main risk factor for type 2 diabetes (T2D). Studies performed over the last 20 years have identified inflammation as the most important link between these two diseases. During the development of obesity, there is activation of subclinical inflammatory activity in tissues involved in metabolism and energy homeostasis. Intracellular serine/threonine kinases activated in response to inflammatory factors can catalyse the inhibitory phosphorylation of key proteins of the insulin-signalling pathway, leading to insulin resistance. Moreover, during the progression of obesity and insulin resistance, the pancreatic islets are also affected by inflammation, contributing to b-cell failure and leading to the onset of T2D. In this review, we will present the main mechanisms involved in the activation of obesity-associated metabolic inflammation and discuss potential therapeutic opportunities that can be developed to treat obesity-associated metabolic diseases.

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Adipocyte Fetuin-A Contributes to Macrophage Migration into Adipose Tissue and Polarization of Macrophages

Cited by 112 publications

References 24 publications

Plasma fetuin-A does not correlate with monocyte TLR4 in humans

Plasma fetuin-A does not correlate with monocyte TLR4 in humans

Metabolic crosstalk between fatty pancreas and fatty liver: effects on local inflammation and insulin secretion

MECHANISMS IN ENDOCRINOLOGY: Metabolic and inflammatory pathways on the pathogenesis of type 2 diabetes

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