Transglutaminases and Obesity in Humans: Association of F13A1 to Adipocyte Hypertrophy and Adipose Tissue Immune Response

Transglutaminases TG2 and FXIII-A have recently been linked to adipose tissue biology and obesity, however, human studies for TG family members in adipocytes have not been conducted. In this study, we investigated the association of TGM family members to acquired weight gain in a rare set of monozygotic (MZ) twins discordant for body weight, i.e., heavy–lean twin pairs. We report that F13A1 is the only TGM family member showing significantly altered, higher expression in adipose tissue of the heavier twin. Our previous work linked adipocyte F13A1 to increased weight, body fat mass, adipocyte size, and pro-inflammatory pathways. Here, we explored further the link of F13A1 to adipocyte size in the MZ twins via a previously conducted TWA study that was further mined for genes that specifically associate to hypertrophic adipocytes. We report that differential expression of F13A1 (ΔHeavy–Lean) associated with 47 genes which were linked via gene enrichment analysis to immune response, leucocyte and neutrophil activation, as well as cytokine response and signaling. Our work brings further support to the role of F13A1 in the human adipose tissue pathology, suggesting a role in the cascade that links hypertrophic adipocytes with inflammation.

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Release of Inflammatory Mediators by Human Adipose Tissue Is Enhanced in Obesity and Primarily by the Nonfat Cells: A Review

Mediators of Inflammation ◽

10.1155/2010/513948 ◽

2010 ◽

Vol 2010 ◽

pp. 1-20 ◽

Cited By ~ 120

Author(s):

John N. Fain

Keyword(s):

Adipose Tissue ◽

In Vitro Release ◽

Human Adipose Tissue ◽

Fat Cells ◽

Omental Adipose Tissue ◽

Subcutaneous Adipose ◽

Circulating Levels ◽

Pai 1

This paper considers the role of putative adipokines that might be involved in the enhanced inflammatory response of human adipose tissue seen in obesity. Inflammatory adipokines [IL-6, IL-10, ACE, TGFβ1, TNFα, IL-1β, PAI-1, and IL-8] plus one anti-inflammatory [IL-10] adipokine were identified whose circulating levels as well as in vitro release by fat are enhanced in obesity and are primarily released by the nonfat cells of human adipose tissue. In contrast, the circulating levels of leptin and FABP-4 are also enhanced in obesity and they are primarily released by fat cells of human adipose tissue. The relative expression of adipokines and other proteins in human omental as compared to subcutaneous adipose tissue as well as their expression in the nonfat as compared to the fat cells of human omental adipose tissue is also reviewed. The conclusion is that the release of many inflammatory adipokines by adipose tissue is enhanced in obese humans.

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The role of dietary fatty acids for early human adipose tissue growth

American Journal of Clinical Nutrition ◽

10.3945/ajcn.112.040733 ◽

2013 ◽

Vol 98 (2) ◽

pp. 549S-555S ◽

Cited By ~ 27

Author(s):

Hans Hauner ◽

Stefanie Brunner ◽

Ulrike Amann-Gassner

Keyword(s):

Fatty Acids ◽

Adipose Tissue ◽

Human Adipose Tissue ◽

Tissue Growth ◽

Dietary Fatty Acids ◽

Early Human

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Genetic ablation of adipocyte PD-L1 reduces tumor growth but accentuates obesity-associated inflammation

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-000964 ◽

2020 ◽

Vol 8 (2) ◽

pp. e000964 ◽

Cited By ~ 1

Author(s):

Bogang Wu ◽

Huai-Chin Chiang ◽

Xiujie Sun ◽

Bin Yuan ◽

Payal Mitra ◽

...

Keyword(s):

Adipose Tissue ◽

Tumor Growth ◽

Body Weight Gain ◽

High Body Mass Index ◽

Human Adipose Tissue ◽

Mrna Levels ◽

Metabolic Dysfunction ◽

Genetic Ablation ◽

Tumor Immunosuppression

The programmed death-ligand 1 (PD-L1)-dependent immune checkpoint attenuates host immunity and maintains self-tolerance. Imbalance between protective immunity and immunopathology due to altered PD-L1 signaling can lead to autoimmunity or tumor immunosuppression. The role of the PD-L1-dependent checkpoint in non-immune system is less reported. We previously found that white adipocytes highly express PD-L1. Here we show that adipocyte-specific PD-L1 knockout mice exhibit enhanced host anti-tumor immunity against mammary tumors and melanoma with low or no tumor PD-L1. However, adipocyte PD-L1 ablation in tumor-free mice also exacerbates diet-induced body weight gain, pro-inflammatory macrophage infiltration into adipose tissue, and insulin resistance. Low PD-L1 mRNA levels in human adipose tissue correlate with high body mass index and presence of type 2 diabetes. Therefore, our mouse genetic approach unequivocally demonstrates a cell-autonomous function of adipocyte PD-L1 in promoting tumor growth and inhibiting antitumor immunity. In addition, our work uncovers a previously unrecognized role of adipocyte PD-L1 in mitigating obesity-related inflammation and metabolic dysfunction.

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Enhanced nutritionally induced adipose tissue development in mice with stromelysin-1 gene inactivation

Thrombosis and Haemostasis ◽

10.1055/s-0037-1613586 ◽

2003 ◽

Vol 89 (04) ◽

pp. 696-704 ◽

Cited By ~ 41

Author(s):

Erik Maquoi ◽

Diego Demeulemeester ◽

Gabor Vörös ◽

Désire Collen ◽

H. Lijnen

Keyword(s):

Adipose Tissue ◽

Research Society ◽

The Body ◽

Tissue Development ◽

Cholesterol Levels ◽

Fat Deposits ◽

Adipose Tissue Development ◽

Adipocyte Hypertrophy ◽

Deficient Mice

SummaryTo investigate a potential role of stromelysin-1 (MMP-3) in development of adipose tissue, 5 week old male MMP-3 deficient mice (MMP-3-/-) and wild-type (MMP-3+/+) controls were kept on a high fat diet (HFD) for 15 weeks. MMP-3-/- mice were hyperphagic and gained more weight than the MMP-3+/+ mice. At the time of sacrifice, the body weight of the MMP-3-/- mice was significantly higher than that of the MMP-3+/+ mice, as was the weight of the isolated subcutaneous (SC) and gonadal (GON) fat deposits. Significant adipocyte hypertrophy was observed in the GON but not in the SC adipose tissue of MMP-3-/- mice. Fasting plasma glucose and cholesterol levels were comparable in both genotypes, whereas triglyceride levels were significantly lower in MMP-3-/- mice. Staining with an endothelial cell specific lectin revealed a significantly higher blood vessel density and larger total stained area in the GON adipose tissues of MMP-3-/- mice. Thus, in a murine model of nutritionally induced obesity, MMP-3 impairs adipose tissue development, possibly by affecting food intake and/or adipose tissue-related angiogenesis.Theme paper: Part of this paper was originally presented at the joint meetings of the 16th International Congress of the International Society of Fibrinolysis and Proteolysis (ISFP) and the 17th International Fibrinogen Workshop of the International Fibrinogen Research Society (IFRS) held in Munich, Germany, September, 2002.

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Circulating steroid levels as correlates of adipose tissue phenotype in premenopausal women

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2017-0082 ◽

2018 ◽

Vol 0 (0) ◽

Author(s):

Geneviève B. Marchand ◽

Anne-Marie Carreau ◽

Sofia Laforest ◽

Julie-Anne Côté ◽

Marleen Daris ◽

...

Keyword(s):

Adipose Tissue ◽

Plasma Levels ◽

Subcutaneous Fat ◽

Premenopausal Women ◽

Fat Distribution ◽

Adipocyte Size ◽

Fat Percentage ◽

Potential Marker ◽

Liquid Chromatography Tandem Mass ◽

Adipocyte Hypertrophy

AbstractBackgroundObesity-related alterations in the circulating steroid hormone profile remain equivocal in women. Our objective was to identify circulating steroid levels that relate to increased adiposity and altered adipose phenotype in premenopausal women.Materials and methodsIn a sample of 42 premenopausal women [age 46 ± 3 years; body mass index (BMI) 27.1 ± 4.2 kg/m2], 19 plasma steroids were quantified by electrospray ionization-liquid chromatography-tandem mass spectroscopy (ESI-LC-MS/MS). Body composition and fat distribution were assessed by dual-energy X-ray absorptiometry (DXA) and computed tomography (CT), respectively. Markers of adipose tissue function including adipocyte size distributions, radiological attenuation and macrophage infiltration were also analyzed in surgically obtained visceral and subcutaneous fat samples.ResultsMany negative correlations were observed between adiposity measurements such as BMI, body fat percentage or total abdominal adipose tissue area and plasma levels of androstenedione (Δ4) (r = −0.33 to −0.39, p ≤ 0.04), androsterone (ADT) (r = −0.30 to −0.38, p ≤ 0.05) and steroid precursor pregnenolone (PREG) (r = −0.36 to −0.46, p ≤ 0.02). Visceral adipocyte hypertrophy was observed in patients with low PREG concentrations (p < 0.05). Visceral adipose tissue radiologic attenuation, a potential marker of adipocyte size, was also positively correlated with PREG levels (r = 0.33, p < 0.05). Low levels of PREG were related to increased number of macrophages infiltrating visceral and subcutaneous adipose tissue (p < 0.05).ConclusionPlasma levels of androgens and their precursors are lower in women with increased adiposity and visceral adipocyte hypertrophy. Low circulating PREG concentration may represent a marker of adipose tissue dysfunction.

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