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TL1A regulates adipose-resident innate lymphoid immune responses and enables diet-induced obesity in mice

(2020) INTERNATIONAL JOURNAL OF OBESITY. 44(5). p.1062-1074
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Abstract
Background/objectives: TL1A is a pro-inflammatory cytokine that is homologous to TNF alpha and connected with the development of several chronic inflammatory disorders. The preliminary results of this study indicated reduced fat accumulation in 9-month-old TL1A-deficient mice at steady state. Thus, the objective was to investigate whether TL1A-deficient mice are resistant to the development of high-fat (HF) diet-induced obesity and to investigate the impact on lymphocyte infiltration in adipose tissue. Methods: TL1A-deficient and TL1A-sufficient male BALB/cJ littermate mice were fed a 60% HF diet or a 10% low-fat control diet for 22 weeks. Mouse body composition and weight were monitored, and tissues were processed and evaluated by flow cytometry, qPCR, and histology. Results: In this study, the TL1A-deficient HF-diet-fed mice had reduced whole-body weight gain, which was directly explained by a corresponding fat mass reduction (average 37.2%), compared with that of their TL1A-sufficient littermates. Despite previous data showing marked changes in the gut microbial community, TL1A-deficient GF mice also displayed reduced adiposity. Furthermore, the TL1A-deficient mice were resistant to hepatic steatosis and were shown to have improved glucose tolerance, as determined by oral glucose tolerance test (OGTT), and greater insulin sensitivity. In the epididymal white adipose tissue (eWAT), TL1A deficiency in HF-diet-fed mice resulted in a reduced abundance of IL-18Ra(+) type-1 ILCs and gamma delta T cells as well as markedly reduced expression of the mitochondria-regulating genes Ucp1, Ucp2, Ucp3, and Prdm16. Finally, to investigate the link of TL1A to obesity in humans, we identified a noncoding polymorphism (rs4979453) close to the TL1A locus that is associated with waist circumference in men (p = 0.00096, n = 60586). Conclusions: These findings indicate that TL1A plays an important role in regulating adipose tissue mass and that this role is independent of the gut microbiota. Furthermore, we show that TL1A regulates adipose-resident innate lymphocytes and mitochondria-mediated oxidative stress in eWAT.
Keywords
NECROSIS-FACTOR-ALPHA, CYTOKINE 1A TL1A, INSULIN-RESISTANCE, TNF-ALPHA, INTRAEPITHELIAL LYMPHOCYTES, UNCOUPLING PROTEINS, RECEPTORS DR3, T-CELLS, TISSUE, INFLAMMATION

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MLA
Tougaard, Peter, et al. “TL1A Regulates Adipose-Resident Innate Lymphoid Immune Responses and Enables Diet-Induced Obesity in Mice.” INTERNATIONAL JOURNAL OF OBESITY, vol. 44, no. 5, 2020, pp. 1062–74, doi:10.1038/s41366-020-0539-1.
APA
Tougaard, P., Martinsen, L. O., Luetzhoft, D. O., Jensen, H. E., Flethoj, M., Vandenabeele, P., … Hansen, C. H. F. (2020). TL1A regulates adipose-resident innate lymphoid immune responses and enables diet-induced obesity in mice. INTERNATIONAL JOURNAL OF OBESITY, 44(5), 1062–1074. https://doi.org/10.1038/s41366-020-0539-1
Chicago author-date
Tougaard, Peter, Louise Otterstrom Martinsen, Ditte Olsen Luetzhoft, Henrik Elvang Jensen, Mette Flethoj, Peter Vandenabeele, Anders Elm Pedersen, Soren Skov, Axel Kornerup Hansen, and Camilla Hartmann Friis Hansen. 2020. “TL1A Regulates Adipose-Resident Innate Lymphoid Immune Responses and Enables Diet-Induced Obesity in Mice.” INTERNATIONAL JOURNAL OF OBESITY 44 (5): 1062–74. https://doi.org/10.1038/s41366-020-0539-1.
Chicago author-date (all authors)
Tougaard, Peter, Louise Otterstrom Martinsen, Ditte Olsen Luetzhoft, Henrik Elvang Jensen, Mette Flethoj, Peter Vandenabeele, Anders Elm Pedersen, Soren Skov, Axel Kornerup Hansen, and Camilla Hartmann Friis Hansen. 2020. “TL1A Regulates Adipose-Resident Innate Lymphoid Immune Responses and Enables Diet-Induced Obesity in Mice.” INTERNATIONAL JOURNAL OF OBESITY 44 (5): 1062–1074. doi:10.1038/s41366-020-0539-1.
Vancouver
1.
Tougaard P, Martinsen LO, Luetzhoft DO, Jensen HE, Flethoj M, Vandenabeele P, et al. TL1A regulates adipose-resident innate lymphoid immune responses and enables diet-induced obesity in mice. INTERNATIONAL JOURNAL OF OBESITY. 2020;44(5):1062–74.
IEEE
[1]
P. Tougaard et al., “TL1A regulates adipose-resident innate lymphoid immune responses and enables diet-induced obesity in mice,” INTERNATIONAL JOURNAL OF OBESITY, vol. 44, no. 5, pp. 1062–1074, 2020.
@article{8650488,
  abstract     = {{Background/objectives: TL1A is a pro-inflammatory cytokine that is homologous to TNF alpha and connected with the development of several chronic inflammatory disorders. The preliminary results of this study indicated reduced fat accumulation in 9-month-old TL1A-deficient mice at steady state. Thus, the objective was to investigate whether TL1A-deficient mice are resistant to the development of high-fat (HF) diet-induced obesity and to investigate the impact on lymphocyte infiltration in adipose tissue.
Methods: TL1A-deficient and TL1A-sufficient male BALB/cJ littermate mice were fed a 60% HF diet or a 10% low-fat control diet for 22 weeks. Mouse body composition and weight were monitored, and tissues were processed and evaluated by flow cytometry, qPCR, and histology.
Results: In this study, the TL1A-deficient HF-diet-fed mice had reduced whole-body weight gain, which was directly explained by a corresponding fat mass reduction (average 37.2%), compared with that of their TL1A-sufficient littermates. Despite previous data showing marked changes in the gut microbial community, TL1A-deficient GF mice also displayed reduced adiposity. Furthermore, the TL1A-deficient mice were resistant to hepatic steatosis and were shown to have improved glucose tolerance, as determined by oral glucose tolerance test (OGTT), and greater insulin sensitivity. In the epididymal white adipose tissue (eWAT), TL1A deficiency in HF-diet-fed mice resulted in a reduced abundance of IL-18Ra(+) type-1 ILCs and gamma delta T cells as well as markedly reduced expression of the mitochondria-regulating genes Ucp1, Ucp2, Ucp3, and Prdm16. Finally, to investigate the link of TL1A to obesity in humans, we identified a noncoding polymorphism (rs4979453) close to the TL1A locus that is associated with waist circumference in men (p = 0.00096, n = 60586).
Conclusions: These findings indicate that TL1A plays an important role in regulating adipose tissue mass and that this role is independent of the gut microbiota. Furthermore, we show that TL1A regulates adipose-resident innate lymphocytes and mitochondria-mediated oxidative stress in eWAT.}},
  author       = {{Tougaard, Peter and Martinsen, Louise Otterstrom and Luetzhoft, Ditte Olsen and Jensen, Henrik Elvang and Flethoj, Mette and Vandenabeele, Peter and Pedersen, Anders Elm and Skov, Soren and Hansen, Axel Kornerup and Hansen, Camilla Hartmann Friis}},
  issn         = {{0307-0565}},
  journal      = {{INTERNATIONAL JOURNAL OF OBESITY}},
  keywords     = {{NECROSIS-FACTOR-ALPHA,CYTOKINE 1A TL1A,INSULIN-RESISTANCE,TNF-ALPHA,INTRAEPITHELIAL LYMPHOCYTES,UNCOUPLING PROTEINS,RECEPTORS DR3,T-CELLS,TISSUE,INFLAMMATION}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{1062--1074}},
  title        = {{TL1A regulates adipose-resident innate lymphoid immune responses and enables diet-induced obesity in mice}},
  url          = {{http://doi.org/10.1038/s41366-020-0539-1}},
  volume       = {{44}},
  year         = {{2020}},
}

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