Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity

Hénégar, Corneliu; Tordjman, Joan; Achard, Vincent; Lacasa, Danièle; Cremer, Isabelle; Guerre-Millo, Michéle; Poitou, Christine; Basdevant, Arnaud; Štich, Vladimír; Viguerie, Nathalie; Langin, Dominique; Bédossa, Pierre; Zucker, Jean-Daniel; Clément, Karine

doi:10.1186/gb-2008-9-1-r14

Cited by 393 publications

(344 citation statements)

References 82 publications

(90 reference statements)

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“…Such proximity, already reported in adipose tissue [15], was observed in co-culture experiments (Fig. 7a) between lymphocyte and mature but undifferentiated adipocytes, and no dissociation was seen after washing.…”

Section: Lymphocyte-conditioned Media Alter Adipocyte Behavioursupporting

confidence: 82%

“…CD40L is produced by activated CD4 + T cells [14]. Obesity in mice and humans has been associated recently with T cell accumulation in adipose tissue [15][16][17][18]. In obese mice, accumulation of proinflammatory T lymphocytes in visceral adipose tissue precedes the appearance of macrophages, suggesting that T lymphocytes play an important part in the initiation of adipose tissue inflammation, as well as in the development of insulin resistance [16].…”

Section: Introductionmentioning

confidence: 99%

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The inflammatory receptor CD40 is expressed on human adipocytes: contribution to crosstalk between lymphocytes and adipocytes

et al. 2009

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Aims/hypothesis Obesity is associated with adipose tissue inflammation. The CD40 molecule, TNF receptor superfamily member 5 (CD40)/CD40 ligand (CD40L) pathway plays a role in the onset and maintenance of the inflammatory reaction, but has not been studied in human adipose tissue. Our aim was to examine CD40 expression by human adipocytes and its participation in adipose tissue inflammation. Methods CD40 expression was investigated in human whole adipose tissue and during adipocyte differentiation by real-time PCR, Western blot and immunohistochemistry. The CD40/CD40L pathway was studied using recombinant CD40L (rCD40L) in adipocyte culture and neutralising antibodies in lymphocyte/adipocyte co-culture. Results CD40 mRNA levels in subcutaneous adipose tissue were higher in the adipocyte than in the stromal-vascular fraction. CD40 expression was upregulated during adipocyte differentiation. Addition of rCD40L to adipocytes induced mitogen activated protein kinase (MAPK) activation, stimulated inflammatory adipocytokine production, and decreased insulin-induced glucose transport in parallel with a downregulation of IRS1 and GLUT4 (also known as SCL2A4). rCD40L decreased the expression of lipogenic genes and increased lipolysis. CD40 mRNA levels were significantly higher in subcutaneous adipose tissue than in visceral adipose tissue of obese patients and were positively correlated with BMI, and with IL6 and leptin mRNA levels. Lymphocyte/adipocyte co-culture led to an upregulation of proinflammatory adipocytokines and a downregulation of leptin and adiponectin. Physical separation of the two cell types attenuated these effects, suggesting the involvement of a cell-cell contact. Blocking the CD40/CD40L interaction with neutralising antibodies reduced IL-6 secretion from adipocytes. Conclusions/interpretation Adipocyte CD40 may contribute to obesity-related inflammation and insulin resistance. T lymphocytes regulate adipocytokine production through both the release of soluble factor(s) and heterotypic contact with adipocytes involving CD40.

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Section: Lymphocyte-conditioned Media Alter Adipocyte Behavioursupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

The inflammatory receptor CD40 is expressed on human adipocytes: contribution to crosstalk between lymphocytes and adipocytes

et al. 2009

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“…One such process has also been described to be the end point of a persisting inflammatory stimulus (unresolved chronic inflammation) in AT, which may be responsible for the excessive synthesis of ECM components and subsequent interstitial deposition of fibrotic material 44, 45. There are, however, no studies, to our knowledge, that describe the nature of the inflammatory infiltrate in the AT of cachectic patients.…”

Section: Discussionmentioning

confidence: 99%

Cachexia-associated adipose tissue morphological rearrangement in gastrointestinal cancer patients

Batista

Henriques

Neves

et al. 2015

Journal of Cachexia, Sarcopenia and Muscle

106

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Background and aimsCachexia is a syndrome characterized by marked involuntary loss of body weight. Recently, adipose tissue (AT) wasting has been shown to occur before the appearance of other classical cachexia markers. We investigated the composition and rearrangement of the extracellular matrix, adipocyte morphology and inflammation in the subcutaneous AT (scAT) pad of gastrointestinal cancer patients.MethodsSurgical biopsies for scAT were obtained from gastrointestinal cancer patients, who were signed up into the following groups: cancer cachexia (CC, n = 11), weight‐stable cancer (WSC, n = 9) and weight‐stable control (non‐cancer) (control, n = 7). The stable weight groups were considered as those with no important weight change during the last year and body mass index <25 kg/m2. Subcutaneous AT fibrosis was quantified and characterized by quantitative PCR, histological analysis and immunohistochemistry.ResultsThe degree of fibrosis and the distribution and collagen types (I and III) were different in WSC and CC patients. CC patients showed more pronounced fibrosis in comparison with WSC. Infiltrating macrophages surrounding adipocytes and CD3 Ly were found in the fibrotic areas of scAT. Subcutaneous AT fibrotic areas demonstrated increased monocyte chemotactic protein 1 (MCP‐1) and Cluster of Differentiation (CD)68 gene expression in cancer patients.ConclusionsOur data indicate architectural modification consisting of fibrosis and inflammatory cell infiltration in scAT as induced by cachexia in gastrointestinal cancer patients. The latter was characterized by the presence of macrophages and lymphocytes, more evident in the fibrotic areas. In addition, increased MCP‐1 and CD68 gene expression in scAT from cancer patients may indicate an important role of these markers in the early phases of cancer.

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“…Immunohistochemical analyses Subcutaneous WAT samples were prepared for immunohistochemical analyses as described in the ESM Methods and elsewhere [27,28].…”

Section: Clinical Cohortsmentioning

confidence: 99%

Semaphorin 3C is a novel adipokine linked to extracellular matrix composition

et al. 2013

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Aims/hypothesis Alterations in white adipose tissue (WAT) function, including changes in protein (adipokine) secretion and extracellular matrix (ECM) composition, promote an insulin-resistant state. We set out to identify novel adipokines regulated by body fat mass in human subcutaneous WAT with potential roles in adipose function. Methods Adipose transcriptome data and secretome profiles from conditions with increased/decreased WAT mass were combined. WAT donors were predominantly women. In vitro effects were assessed using recombinant protein. Results were confirmed by quantitative PCR/ELISA, metabolic assays and immunochemistry in human WAT and adipocytes. Results We identified a hitherto uncharacterised adipokine, semaphorin 3C (SEMA3C), the expression of which correlated significantly with body weight, insulin resistance (HOMA of insulin resistance [HOMA IR ], and the rate constant for the insulin tolerance test [K ITT ]) and adipose tissue morphology (hypertrophy vs hyperplasia). SEMA3C was primarily found in mature adipocytes and had no direct effect on human adipocyte differentiation, lipolysis, glucose transport or the expression of β-oxidation genes. This could in part Electronic supplementary material The online version of this article

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Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity

Cited by 393 publications

References 82 publications

The inflammatory receptor CD40 is expressed on human adipocytes: contribution to crosstalk between lymphocytes and adipocytes

The inflammatory receptor CD40 is expressed on human adipocytes: contribution to crosstalk between lymphocytes and adipocytes

Cachexia-associated adipose tissue morphological rearrangement in gastrointestinal cancer patients

Semaphorin 3C is a novel adipokine linked to extracellular matrix composition

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