NFκB as a potent regulator of inflammation in human adipose tissue, influenced by depot, adiposity, T2DM status, and TNFα

Harte, Alison; Tripathi, Gyanendra; Piya, Milan K.; Barber, Thomas M.; Clapham, John C.; Al-Daghri, Nasser M.; Aldisi, Dara; Kumsaiyai, Warunee; Saravanan, Ponnusamy; Fowler, Anne E; O’Hare, J. Paul; Kumar, Sudhesh; McTernan, P. G.

doi:10.1002/oby.20336

Cited by 17 publications

(16 citation statements)

References 40 publications

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“…In particular visceral AT, including omental adipose tissue (OAT), is associated with adverse metabolic consequences of obesity . Besides expansion of (O)AT, obesity coincides with adipose tissue (AT)‐inflammation, characterized by hypertrophic adipocytes, increased influx of immune cells, and inflammasome activation . Subsequent disproportionate pro‐inflammatory adipokine secretion elicits a local immune response, propagated by communication between adipocytes and macrophages, generating a self‐sustaining reciprocal pro‐inflammatory loop .…”

Section: Introductionmentioning

confidence: 99%

Human adipocyte extracellular vesicles in reciprocal signaling between adipocytes and macrophages

Kranendonk

Visseren

Balkom

et al. 2014

Obesity

158

148

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Objective: Extracellular vesicles (EVs) released by human adipocytes or adipose tissue (AT)-explants play a role in the paracrine interaction between adipocytes and macrophages, a key mechanism in AT inflammation, leading to metabolic complications like insulin resistance (IR) were determined. Methods: EVs released from in vitro differentiated adipocytes and AT-explants ex vivo were characterized by electron microscopy, Western blot, multiplex adipokine-profiling, and quantified by flow cytometry. Primary monocytes were stimulated with EVs from adipocytes, subcutaneous (SCAT) or omental-derived AT (OAT), and phenotyped. Macrophage supernatant was subsequently used to assess the effect on insulin signaling in adipocytes.Results: Adipocyte and AT-derived EVs differentiated monocytes into macrophages characteristic of human adipose tissue macrophages (ATM), defined by release of both pro-and anti-inflammatory cytokines. The adiponectin-positive subset of AT-derived EVs, presumably representing adipocyte-derived EVs, induced a more pronounced ATM-phenotype than the adiponectin-negative AT-EVs. This effect was more evident for OAT-EVs versus SCAT-EVs. Furthermore, supernatant of macrophages pre-stimulated with AT-EVs interfered with insulin signaling in human adipocytes. Finally, the number of OAT-derived EVs correlated positively with patients HOMA-IR. Conclusions: A possible role for human AT-EVs in a reciprocal pro-inflammatory loop between adipocytes and macrophages, with the potential to aggravate local and systemic IR was demonstrated.

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Section: Introductionmentioning

confidence: 99%

Human adipocyte extracellular vesicles in reciprocal signaling between adipocytes and macrophages

Kranendonk

Visseren

Balkom

et al. 2014

Obesity

158

148

View full text Add to dashboard Cite

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“…It is known that NF‐κB is important in the process of insulin resistance 38 and T2D 39. It has been shown that CARD9‐deficient cells are defective in zymosan‐induced NF‐κB activation 3.…”

Section: Discussionmentioning

confidence: 99%

“…The activation of NF-jB and other transcription factors further induce the expression of various cytokines and chemokines and inflammatory responses. It is known that NF-jB is important in the process of insulin resistance [38] and T2D [39]. It has been shown that CARD9-deficient cells are defective in zymosan-induced NF-jB activation [3].…”

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confidence: 99%

The essential function of CARD9 in diet‐induced inflammation and metabolic disorders in mice

Zeng

Zhang

et al. 2018

J Cellular Molecular Medi

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Inflammation and metabolic disorder are common pathophysiological conditions, which play a vital role in the development of obesity and type 2 diabetes. The purpose of this study was to explore the effects of caspase recruitment domain (CARD) 9 in the high fat diet (HFD)‐treated mice and attempt to find a molecular therapeutic target for obesity development and treatment. Sixteen male CARD9−/− and corresponding male WT mice were fed with normal diet or high fat diet, respectively, for 12 weeks. Glucose tolerance, insulin resistance, oxygen consumption and heat production of the mice were detected. The CARD9/MAPK pathway‐related gene and protein were determined in insulin‐responsive organs using Western blotting and quantitative PCR. The results showed that HFD‐induced insulin resistance and impairment of glucose tolerance were more severe in WT mice than that in the CARD9−/− mice. CARD9 absence significantly modified O2 consumption, CO 2 production and heat production. CARD9−/− mice displayed the lower expression of p38 MAPK, JNK and ERK when compared to the WT mice in both HFD‐ and ND‐treated groups. HFD induced the increase of p38 MAPK, JNK and ERK in WT mice but not in the CARD9−/− mice. The results indicated that CARD9 absence could be a vital protective factor in diet‐induced obesity via the CARD9/MAPK pathway, which may provide new insights into the development of gene knockout to improving diet‐induced obesity and metabolism disorder.

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“…The nonsignificant differences are attributed to the small size number of participants. Previous studies mentioned that several inflammatory biomarkers are increased in obesity and many authors believed that these proinflammatory markers played a role in the etiology of obesity [4,5,6]. C-reactive protein was strongly related to total and central abdominal obesity, blood pressure, and lipid levels, independent of genetic influences [7].…”

Section: Discussionmentioning

confidence: 99%

Are obese women potential for inflammatory process? A pilot study

Journal¹

2014

Baghdad Sci.J

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This study was designed to look for certain biochemical markers(serum uric acid and serum peroxynitrite) in women presented with obesity and to compare the level of these markers with non-obese women. A total number of 63 women were recruited from outpatients and private clinics to admit in this study. The patients were grouped into non obese women (Group I) and obese women (Group II). The anthropometric and blood pressure were determined and venous blood was obtained from each patient for determination of C-reactive protein, uric acid and peroxynitrite. The results showed that there were no significant differences in age or in concomitant or associated diseases in both groups except rheumatoid arthritis which account 80% of group I and 25% of group II. The body mass index of Group I patients was 25.27±4.19 kg/h2 compared with 40.03±16.64 kg/h2 of Group II (p < 0.001). There were no significant differences in waist to hip ratio between two groups. The means systolic and diastolic blood pressures were higher in Group II compare with Group I. Positive C-reactive protein was observed in 53.3% and 52.1% of patients in Groups I and II respectively. Serum uric acid and peroxynitrite were non-significantly higher in Group II compared with Group I. It was concluded that obesity in women is associated with increased level of metabolic and nitrosative markers as well as alteration in inflammatory marker.

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NFκB as a potent regulator of inflammation in human adipose tissue, influenced by depot, adiposity, T2DM status, and TNFα

Cited by 17 publications

References 40 publications

Human adipocyte extracellular vesicles in reciprocal signaling between adipocytes and macrophages

Human adipocyte extracellular vesicles in reciprocal signaling between adipocytes and macrophages

The essential function of CARD9 in diet‐induced inflammation and metabolic disorders in mice

Are obese women potential for inflammatory process? A pilot study

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