scholarly journals Obesity accelerates T cell senescence in murine visceral adipose tissue

2016 ◽  
Vol 126 (12) ◽  
pp. 4626-4639 ◽  
Author(s):  
Kohsuke Shirakawa ◽  
Xiaoxiang Yan ◽  
Ken Shinmura ◽  
Jin Endo ◽  
Masaharu Kataoka ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
T Cell ◽  
Visceral Adipose Tissue ◽  
Cell Senescence ◽  
Visceral Adipose ◽  
T Cell Senescence

Abstract 11105: Obesity Accelerates T Cell Senescence in Visceral Adipose Tissue

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Kohsuke Shirakawa ◽  
Ken Shinmura ◽  
Jin Endo ◽  
Masaharu Kataoka ◽  
Tsunehisa Yamamoto ◽  
...  
Keyword(s):  
T Cells ◽  
Adipose Tissue ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cell Senescence ◽  
Immune Senescence ◽  
Obese Mice ◽  
Adipose Inflammation ◽  
Visceral Adipose ◽  
T Cell Senescence

Background: Age-related changes in the immune function, particularly T-cell immune-senescence likely contribute to the nature of chronic inflammation associated with ageing-related diseases. Recently, it becomes clear that T-cell immune-senescence is not due to dysregulation of the whole T cell population, but rather the accumulation of senescence-associated T-cells. The senescence-associated T-cells are memory phenotype (MP) T-cells that constitutively express programmed cell death 1 (PD-1) on their surface. Purpose: Obesity predisposes to a lower age of onset of ageing-related diseases. We examined whether obesity accelerates T-cell senescence in visceral adipose tissue (VAT), and if so, how this impacts on VAT inflammation and glucose metabolism. Results: HFD-induced obesity causes the phenotypic changes in CD4+ T-cells similar to those observed during chronological aging process, marked by a progress increase in the number of PD-1+ MP CD4+ T-cells highly resembling senescence-associated T cells. Unique features of adipose tissue PD-1+ MP CD4+ T-cells include; expression of myeloid lineage gene, attenuated TCR-mediated proliferation, a decreased ability to produce T-cell specific lymphokines on TCR stimulation, highly biased secretin of OPN, and a rise in the levels of DNA damage response markers as well as the cyclin-dependent kinase inhibitors. The PD-1+ MP CD4+ T-cells stimulated macrophage infiltration and promoted M1 macrophage polarization, while reducing regulatory T-cells in VAT. HFD-dependent conversion of naïve T cells to PD-1+ MP T-cells in VAT depends on macrophages and B cells. Immunological depletion of PD-1+ T-cells attenuated adipose inflammation and improved insulin resistance in diet-induced obese mice, while adoptive transfer of PD-1+ MP CD4+ T-cells in VAT induced adipose inflammation and insulin resistance in non-obese mice. Analysis of human tissue suggested that a similar process may also occur in human. Interestingly, T2DM patients had more abundant PD-1+ T-cells in omental adipose tissue than non-DM patients independently BMI and age. Conclusion: Increased visceral adiposity accelerates T-cell senescence and this, in turn, leads to chronic VAT inflammation and abnormal glucose metabolism.

scholarly journals CD8+ T Cells Involved in Metabolic Inflammation in Visceral Adipose Tissue and Liver of Transgenic Pigs

2021 ◽  
Vol 12 ◽  
Author(s):  
Kaiyi Zhang ◽  
Cong Tao ◽  
Jianping Xu ◽  
Jinxue Ruan ◽  
Jihan Xia ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
T Cell ◽  
Visceral Adipose Tissue ◽  
Antigen Processing ◽  
Metabolic Diseases ◽  
Early Stage ◽  
Large Animal ◽  
Transgenic Pigs ◽  
Inflammatory Signaling ◽  
Visceral Adipose

Anti-inflammatory therapies have the potential to become an effective treatment for obesity-related diseases. However, the huge gap of immune system between human and rodent leads to limitations of drug discovery. This work aims at constructing a transgenic pig model with higher risk of metabolic diseases and outlining the immune responses at the early stage of metaflammation by transcriptomic strategy. We used CRISPR/Cas9 techniques to targeted knock-in three humanized disease risk genes, GIPRdn, hIAPP and PNPLA3I148M. Transgenic effect increased the risk of metabolic disorders. Triple-transgenic pigs with short-term diet intervention showed early symptoms of type 2 diabetes, including glucose intolerance, pancreatic lipid infiltration, islet hypertrophy, hepatic lobular inflammation and adipose tissue inflammation. Molecular pathways related to CD8+ T cell function were significantly activated in the liver and visceral adipose samples from triple-transgenic pigs, including antigen processing and presentation, T-cell receptor signaling, co-stimulation, cytotoxicity, and cytokine and chemokine secretion. The similar pro-inflammatory signaling in liver and visceral adipose tissue indicated that there might be a potential immune crosstalk between the two tissues. Moreover, genes that functionally related to liver antioxidant activity, mitochondrial function and extracellular matrix showed distinct expression between the two groups, indicating metabolic stress in transgenic pigs’ liver samples. We confirmed that triple-transgenic pigs had high coincidence with human metabolic diseases, especially in the scope of inflammatory signaling at early stage metaflammation. Taken together, this study provides a valuable large animal model for the clinical study of metaflammation and metabolic diseases.

scholarly journals Distinct Blood and Visceral Adipose Tissue Regulatory T Cell and Innate Lymphocyte Profiles Characterize Obesity and Colorectal Cancer

2017 ◽  
Vol 8 ◽  
Author(s):  
Gloria Donninelli ◽  
Manuela Del Cornò ◽  
Marina Pierdominici ◽  
Beatrice Scazzocchio ◽  
Rosaria Varì ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adipose Tissue ◽  
T Cell ◽  
Visceral Adipose Tissue ◽  
Regulatory T Cell ◽  
Visceral Adipose

scholarly journals The effect of caloric restriction on the increase in senescence-associated T cells and metabolic disorders in aged mice

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252547
Author(s):  
Xiaoxiang Yan ◽  
Natsumi Imano ◽  
Kayoko Tamaki ◽  
Motoaki Sano ◽  
Ken Shinmura
Keyword(s):  
Insulin Resistance ◽  
T Cells ◽  
Adipose Tissue ◽  
T Cell ◽  
Caloric Restriction ◽  
Visceral Adipose Tissue ◽  
Aged Mice ◽  
Age Related ◽  
Visceral Adipose

Aging is associated with functional decline in the immune system and increases the risk of chronic diseases owing to smoldering inflammation. In the present study, we demonstrated an age-related increase in the accumulation of Programmed Death-1 (PD-1)+ memory-phenotype T cells that are considered “senescence-associated T cells” in both the visceral adipose tissue and spleen. As caloric restriction is an established intervention scientifically proven to exert anti-aging effects and greatly affects physiological and pathophysiological alterations with advanced age, we evaluated the effect of caloric restriction on the increase in this T-cell subpopulation and glucose tolerance in aged mice. Long-term caloric restriction significantly decreased the number of PD-1+ memory-phenotype cluster of differentiation (CD) 4+ and CD8+ T cells in the spleen and visceral adipose tissue, decreased M1-type macrophage accumulation in visceral adipose tissue, and improved insulin resistance in aged mice. Furthermore, the immunological depletion of PD-1+ T cells reduced adipose inflammation and improved insulin resistance in aged mice. Taken together with our previous report, these results indicate that senescence-related T-cell subpopulations are involved in the development of chronic inflammation and insulin resistance in the context of chronological aging and obesity. Thus, long-term caloric restriction and specific deletion of senescence-related T cells are promising interventions to regulate age-related chronic diseases.

scholarly journals ICOS signaling limits regulatory T cell accumulation and function in visceral adipose tissue

2021 ◽  
Vol 218 (6) ◽  
Author(s):  
Kristen L. Mittelsteadt ◽  
Erika T. Hayes ◽  
Daniel J. Campbell
Keyword(s):  
Adipose Tissue ◽  
T Cell ◽  
Insulin Sensitivity ◽  
Visceral Adipose Tissue ◽  
Cell Accumulation ◽  
Elevated Expression ◽  
Phosphoinositide 3 Kinase ◽  
And Function ◽  
Adipose Inflammation ◽  
Visceral Adipose

A unique population of Foxp3+ regulatory T cells (TRs) resides in visceral adipose tissue (VAT) that regulates adipose inflammation and helps preserve insulin sensitivity. Inducible T cell co-stimulator (ICOS) is highly expressed on effector (e)TRs that migrate to nonlymphoid tissues, and contributes to their maintenance and function in models of autoimmunity. In this study, we report an unexpected cell-intrinsic role for ICOS expression and downstream phosphoinositide 3-kinase (PI3K) signaling in limiting the abundance, VAT-associated phenotype, and function of TRs specifically in VAT. Icos−/− mice and mice expressing a knock-in form of ICOS that cannot activate PI3K had increased VAT-TR abundance and elevated expression of canonical VAT-TR markers. Loss of ICOS signaling facilitated enhanced accumulation of TRs to VAT associated with elevated CCR3 expression, and resulted in reduced adipose inflammation and heightened insulin sensitivity in the context of a high-fat diet. Thus, we have uncovered a new and surprising molecular pathway that regulates VAT-TR accumulation and function.

scholarly journals Appearance and disappearance of the mRNA signature characteristic of Tregcells in visceral adipose tissue: Age, diet, and PPARγ effects

2014 ◽  
Vol 112 (2) ◽  
pp. 482-487 ◽  
Author(s):  
Daniela Cipolletta ◽  
Paul Cohen ◽  
Bruce M. Spiegelman ◽  
Christophe Benoist ◽  
Diane Mathis
Keyword(s):  
Adipose Tissue ◽  
T Cell ◽  
Visceral Adipose Tissue ◽  
Obese Mouse ◽  
The Metabolic Syndrome ◽  
Fat Depot ◽  
Visceral Adipose ◽  
High Representation ◽  
Very High

A unique population of Foxp3+CD4+regulatory T (Treg) cells resides in visceral adipose tissue (VAT) of lean mice, especially in the epididymal fat depot. VAT Tregsare unusual in their very high representation within the CD4+T-cell compartment, their transcriptome, and their repertoire of antigen-specific T-cell receptors. They are important regulators of local and systemic inflammation and metabolism. The overall goal of this study was to learn how the VAT Tregtranscriptome adapts to different stimuli; in particular, its response to aging in lean mice, to metabolic perturbations associated with obesity, and to certain signaling events routed through PPARγ, the “master-regulator” of adipocyte differentiation. We show that the VAT Tregsignature is imposed early in life, well before age-dependent expansion of the adipose-tissue Tregpopulation. VAT Tregsin obese mice lose the signature typical of lean individuals but gain an additional set of over- and underrepresented transcripts. This obese mouse VAT Tregsignature depends on phosphorylation of the serine residue at position 273 of PPARγ, in striking parallel to a pathway recently elucidated in adipocytes. These findings are important to consider in designing drugs to target type 2 diabetes and other features of the “metabolic syndrome.”

Lack of association between colorectal adenoma recurrence and visceral adipose tissue

2001 ◽  
Vol 120 (5) ◽  
pp. A254-A254
Author(s):  
D SASS ◽  
R SCHOEN ◽  
J WEISSFELD ◽  
L KULLER ◽  
F THAETE ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Colorectal Adenoma ◽  
Visceral Adipose Tissue ◽  
Adenoma Recurrence ◽  
Colorectal Adenoma Recurrence ◽  
Visceral Adipose
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