Increased Tenascin C And Toll-Like Receptor 4 Levels in Visceral Adipose Tissue as a Link between Inflammation and Extracellular Matrix Remodeling in Obesity

Catalán, Victoria; Gómez-Ambrosi, Javier; Rodríguez, Amaia; Ramírez, Beatriz; Rotellar, Fernando; Valentí, Víctor; Silva, Camilo; Gil, Marı́a J.; Salvador, Javier; Frühbeck, Gema

doi:10.1210/jc.2012-1670

Cited by 76 publications

(68 citation statements)

References 51 publications

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“…In agreement with our findings, no differences in the expression of inflammatory genes in peripheral blood mononuclear cells between MHO and MAO groups were found in a recent study (33). In the same line, we found that TNC and MMP9, genes involved in matrix remodeling (21,30), were similarly upregulated in both obese groups, suggesting that VAT remodeling, as suggested by the expression of genes involved in this process, is analogously contributing to adipose expansion in both obesity phenotypes. To analyze the potential contribution of subcutaneous adipose tissue and, in particular, deep abdominal subcutaneous adipose tissue will be of interest in future studies.…”

Section: Resultssupporting

confidence: 62%

“…The primer and probe concentrations for gene amplification were 300 and 200 nmol/L, respectively. All results were normalized to the levels of 18S rRNA (Applied Biosystems), and relative quantification was calculated using the DDCt formula (20,21). Relative mRNA expression was expressed as fold expression over the calibrator sample (average of gene expression corresponding to the lean group in VAT and MHO group in liver).…”

Section: Gene Expression By Real-time Pcrmentioning

confidence: 99%

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Increased Cardiometabolic Risk Factors and Inflammation in Adipose Tissue in Obese Subjects Classified as Metabolically Healthy

et al. 2014

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OBJECTIVEIt has been suggested that individuals with the condition known as metabolically healthy obesity (MHO) may not have the same increased risk for the development of metabolic abnormalities as their non-metabolically healthy counterparts. However, the validity of this concept has recently been challenged, since it may not translate into lower morbidity and mortality. The aim of the current study was to compare the cardiometabolic/inflammatory profile and the prevalence of impaired glucose tolerance (IGT) and type 2 diabetes (T2D) in patients categorized as having MHO or metabolically abnormal obesity (MAO). RESEARCH DESIGN AND METHODSWe performed a cross-sectional analysis to compare the cardiometabolic/inflammatory profile of 222 MHO and 222 MAO patients (62% women) matched by age, including 255 lean subjects as reference (cohort 1). In a second cohort, we analyzed the adipokine profile and the expression of genes involved in inflammation and extracellular matrix remodeling in visceral adipose tissue (VAT; n = 82) and liver (n = 55). RESULTSThe cardiometabolic and inflammatory profiles (CRP, fibrinogen, uric acid, leukocyte count, and hepatic enzymes) were similarly increased in MHO and MAO in both cohorts. Moreover, above 30% of patients classified as MHO according to fasting plasma glucose exhibited IGT or T2D. The profile of classic (leptin, adiponectin, resistin) as well as novel (serum amyloid A and matrix metallopeptidase 9) adipokines was almost identical in MHO and MAO groups in cohort 2. Expression of genes involved in inflammation and tissue remodeling in VAT and liver showed a similar alteration pattern in MHO and MAO individuals. CONCLUSIONSThe current study provides evidence for the existence of a comparable adverse cardiometabolic profile in MHO and MAO patients; thus the MHO concept should be applied with caution. A better identification of the obesity phenotypes and a more precise diagnosis are needed for improving the management of obese individuals.

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Section: Resultssupporting

confidence: 62%

Section: Gene Expression By Real-time Pcrmentioning

confidence: 99%

Increased Cardiometabolic Risk Factors and Inflammation in Adipose Tissue in Obese Subjects Classified as Metabolically Healthy

et al. 2014

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“…We confirmed the ability of leptin to stimulate Tnf mRNA expression in murine 3T3-L1 adipocytes, but not in undifferentiated preadipocytes. Interestingly, our data revealed that leptin also promoted the synthesis and release of TNC, an endogenous activator of Toll-like receptor 4 (TLR4) that is key for the production of proinflammatory cytokines and ECM remodeling 19,22 . TNC expression can be induced in adipocytes after stimulation with proinflammatory cytokines and/or by growth factors from activated macrophages 11 , probably via TLR4 22 .…”

Section: Discussionmentioning

confidence: 90%

“…In line with this observation, our data showed that genes involved in the regulation of hypoxic response (Hif1a), inflammation (Tnf, Emr1), and excessive collagen deposition (Col6a1 and Col6a3) were highly enriched in EWAT of leptin-deficient ob/ob mice. Moreover, circulating levels and EWAT expression of the alarmin TNC were also significantly increased in ob/ob mice, contributing to the sustained inflammatory response and ECM remodeling associated to obesity 22 . Our results provide further evidence that in vivo chronic leptin administration reverted obesity, metabolic disturbances, as well as reduced the expression of hypoxic, proinflammatory and profibrotic genes.…”

Section: Discussionmentioning

confidence: 99%

“…TNC is associated with tissue injury as well as inflammation and modulates fibrotic and inflammatory responses in diverse diseases, such as liver fibrosis, arthritis, or obesity by inducing the production of proinflammatory cytokines [19][20][21] . Our group has recently described that TNC participates in the etiopathology of obesity via AT inflammation 22 .…”

Section: Introductionmentioning

confidence: 99%

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Targeted disruption of the iNOS gene improves adipose tissue inflammation and fibrosis in leptin-deficient ob/ob mice: role of tenascin C

et al. 2018

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Background/Objectives: Obesity is related to a dynamic extracellular matrix (ECM) remodeling, which involves the synthesis and degradation of different proteins, such as tenascin C (TNC) in the adipose tissue (AT). Given the functional relationship between leptin and inducible nitric oxide synthase (iNOS), our aim was to analyze the impact of the absence of the iNOS gene in AT inflammation and ECM remodeling in ob/ob mice. Subjects/Methods: The expression of genes involved in inflammation and ECM remodeling was evaluated in 10-week-old male double knockout (DBKO) mice simultaneously lacking the ob and iNOS genes as well as in ob/ob mice classified into three groups [control, leptin-treated (1 mg kg −1 day −1 ) and pair-fed]. Results: Leptin deficiency increased inflammation and fibrosis in AT. As expected, leptin treatment improved the obesity phenotype. iNOS deficiency in ob/ob mice improved insulin sensitivity, AT inflammation, and ECM remodeling, as evidenced by lower AT macrophage infiltration and collagen deposition, a downregulation of proinflammatory and profibrogenic genes Tnf, Emr1, Hif1a, Col6a1, Col6a3, and Tnc, as well as lower circulating TNC levels. Interestingly, leptin upregulated TNC expression and release in 3T3-L1 adipocytes, and iNOS knockdown in 3T3-L1 fat cells produced a significant decrease in basal and leptin-induced Tnc expression. Conclusions: Ablation of iNOS in leptin-deficient mice improved AT inflammation and ECM remodeling-related genes, attenuating fibrosis, and metabolic dysfunction. The activation of iNOS by leptin is necessary for the synthesis and secretion of TNC in adipocytes, suggesting an important role of this alarmin in the development of AT inflammation and fibrosis.

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Regional Differences Between Perisynovial and Infrapatellar Adipose Tissue Depots and Their Response to Class II and Class III Obesity in Patients With Osteoarthritis

Harasymowicz

Clement

Azfer

et al. 2017

Arthritis & Rheumatology

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Increased Tenascin C And Toll-Like Receptor 4 Levels in Visceral Adipose Tissue as a Link between Inflammation and Extracellular Matrix Remodeling in Obesity

Abstract: These findings indicate that TNC is involved in the etiopathology of obesity via visceral adipose tissue inflammation representing a link with ECM remodeling.

Cited by 76 publications

References 51 publications

Increased Cardiometabolic Risk Factors and Inflammation in Adipose Tissue in Obese Subjects Classified as Metabolically Healthy

Increased Cardiometabolic Risk Factors and Inflammation in Adipose Tissue in Obese Subjects Classified as Metabolically Healthy

Targeted disruption of the iNOS gene improves adipose tissue inflammation and fibrosis in leptin-deficient ob/ob mice: role of tenascin C

Regional Differences Between Perisynovial and Infrapatellar Adipose Tissue Depots and Their Response to Class II and Class III Obesity in Patients With Osteoarthritis

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