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.”

Abstract 17843: Visceral Adipose Tissue Secretion of Adiponectin Decreases with Increased Body Mass Index

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Lenore R Rengel ◽  
Brittaney Obi ◽  
Jon Gould ◽  
Matthew Goldblatt ◽  
Andrew Kastenmeier ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
Metabolic Health ◽  
Metabolically Healthy Obese ◽  
Obese Subjects ◽  
Healthy Obese ◽  
Metabolically Healthy ◽  
Visceral Adipose ◽  
Subcutaneous Adipose

Introduction: Peripheral adiposity is associated with better metabolic health and higher plasma adiponectin (ADPN) levels. Since ADPN is secreted mainly by adipose tissue (AT), it is intriguing that higher visceral adipose tissue (VAT) is associated with lower ADPN levels and poor metabolic health. Hypothesis: We hypothesized that various AT depots differ in their ability to secrete ADPN. Methods: Paired AT samples (VAT and subcutaneous adipose tissue (SAT)) were collected from 19 subjects (10 women, 15 obese) undergoing elective abdominal surgery. The samples were cultured and the supernatant was collected after 24 hours. ADPN levels released into the supernatant from VAT and SAT were measured using multiplex methods. Subjects were defined as obese or non-obese (NO) based on BMI > or ≤ 30kg/m2 respectively. Obese subjects were further classified as metabolically unhealthy obese (MUO) or metabolically healthy obese (MHO) based on presence or absence of type 2 diabetes mellitus, hypertension, or cardiovascular disease at the time of surgery. Results: Mean ADPN secretion levels from SAT and VAT were similar in NO subjects (17.3 ± 3.4 vs. 9.8 ± 13.0 ng/mL/mg, p=0.5) whereas the mean ADPN secretion was lower from VAT among obese subjects (15.9 ± 0.8 vs. 4.5 ± 0.2 ng/mL/mg, p=0.0002). ADPN secretion decreased from VAT (r=-0.16) and increased from SAT (r=0.33) with increased BMI (Fig.1). When MHO and MUO were compared, ADPN secretion from VAT in MHO was reduced only slightly (16.1 ± 8.2 vs. 4.0 ± 2.0 ng/mL/mg, p=0.07) whereas ADPN secretion was significantly reduced in MUO (15.9 ± 5.3 vs. 4.7 ± 4.6 ng/mL/mg, p=0.003). Conclusions: Reduced ADPN secretion from VAT in subjects with increasing BMI may explain lower circulating ADPN levels in obese individuals. Higher ADPN production from SAT and the relatively preserved secretion of ADPN from VAT may explain metabolic health in some obese individuals. Futures studies will help identify factors that control ADPN secretion from AT.

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

Epigenetic Downregulation of FASN in Visceral Adipose Tissue of Insulin Resistant Subjects

2020 ◽  
Author(s):  
Helen Sievert ◽  
Christin Krause ◽  
Cathleen Geißler ◽  
Martina Grohs ◽  
Alexander T. El-Gammal ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Dna Methylation ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Glucose Intolerance ◽  
Visceral Adipose Tissue ◽  
High Hba1c ◽  
Obese Subjects ◽  
Visceral Adipose

Abstract Objective The risk to develop type 2 diabetes increases with the amount of visceral adiposity presumably due to increased lipolysis and subsequent lipid accumulation in visceral organs. However, data describing the molecular regulation of these pathways in humans are rare. We tested if genes of the lipogenic and lipolytic pathways are associated with glucose intolerance independently of obesity in visceral adipose tissue (VAT) of obese subjects. Moreover, we studied DNA methylation of FASN (fatty acid synthase), that catalyses the synthesis of long-chain fatty acids, in VAT of the same subjects and whether it is associated with metabolic traits. Subjects and methods Visceral adipose tissue biopsies and blood samples were taken from 93 severely obese subjects undergoing bariatric surgery. Subjects were grouped in low HbA1c (L-HbA1c, HbA1c<6.5 %) and high HbA1c (H-HbA1c, HbA1c≥6.5 %) groups and expression of genes from the lipogenic and lipolytic pathways was analysed by TaqMan qPCR. DNA methylation of FASN was quantified by bisulfite-pyrosequencing. Results FASN expression was downregulated in visceral fat from subjects with high HbA1c (p = 0.00009). Expression of other lipogenetic (SCD, ELOVL6) or lipolytic genes (ADRB3, PNPLA2) and FABP4 was not changed. DNA methylation of FASN was increased at a regulatory ChoRE recognition site in the H-HbA1c-subgroup and correlated negatively with FASN mRNA (r = − 0.302, p = 0.0034) and positively with HbA1c (r = 0.296, p = 0.0040) and blood glucose (r = 0.363, p = 0.0005). Conclusions Epigenetic downregulation of FASN in visceral adipose tissue of obese subjects might contribute to limited de novo lipogenesis of important insulin sensitizing fatty acids and could thereby contribute to glucose intolerance and the development of type 2 diabetes independently of obesity.

scholarly journals The human type 2 diabetes-specific visceral adipose tissue proteome and transcriptome in obesity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nicholas J. Carruthers ◽  
Clarissa Strieder-Barboza ◽  
Joseph A. Caruso ◽  
Carmen G. Flesher ◽  
Nicki A. Baker ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Visceral Adipose Tissue ◽  
Sequencing Analysis ◽  
Complement Factor ◽  
Endothelial Protein C Receptor ◽  
Visceral Adipose

AbstractDysfunctional visceral adipose tissue (VAT) in obesity is associated with type 2 diabetes (DM) but underlying mechanisms remain unclear. Our objective in this discovery analysis was to identify genes and proteins regulated by DM to elucidate aberrant cellular metabolic and signaling mediators. We performed label-free proteomics and RNA-sequencing analysis of VAT from female bariatric surgery subjects with DM and without DM (NDM). We quantified 1965 protein groups, 23 proteins, and 372 genes that were differently abundant in DM vs. NDM VAT. Proteins downregulated in DM were related to fatty acid synthesis and mitochondrial function (fatty acid synthase, FASN; dihydrolipoyl dehydrogenase, mitochondrial, E3 component, DLD; succinate dehydrogenase-α, SDHA) while proteins upregulated in DM were associated with innate immunity and transcriptional regulation (vitronectin, VTN; endothelial protein C receptor, EPCR; signal transducer and activator of transcription 5B, STAT5B). Transcriptome indicated defects in innate inflammation, lipid metabolism, and extracellular matrix (ECM) function, and components of complement classical and alternative cascades. The VAT proteome and transcriptome shared 13 biological processes impacted by DM, related to complement activation, cell proliferation and migration, ECM organization, lipid metabolism, and gluconeogenesis. Our data revealed a marked effect of DM in downregulating FASN. We also demonstrate enrichment of complement factor B (CFB), coagulation factor XIII A chain (F13A1), thrombospondin 1 (THBS1), and integrins at mRNA and protein levels, albeit with lower q-values and lack of Western blot or PCR confirmation. Our findings suggest putative mechanisms of VAT dysfunction in DM.

scholarly journals Progression from High Insulin Resistance to Type 2 Diabetes Does Not Entail Additional Visceral Adipose Tissue Inflammation

PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e48155 ◽  
Author(s):  
Nuria Barbarroja ◽  
Chary Lopez-Pedrera ◽  
Lourdes Garrido-Sanchez ◽  
Maria Dolores Mayas ◽  
Wilfredo Oliva-Olivera ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
Adipose Tissue Inflammation ◽  
Tissue Inflammation ◽  
High Insulin ◽  
Visceral Adipose
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