scholarly journals Single-Cell RNA Sequencing of Visceral Adipose Tissue Leukocytes Reveals that Caloric Restriction Following Obesity Promotes the Accumulation of a Distinct Macrophage Population with Features of Phagocytic Cells

2019 ◽  
Keyword(s):  
Adipose Tissue ◽  
Single Cell ◽  
Rna Sequencing ◽  
Caloric Restriction ◽  
Visceral Adipose Tissue ◽  
Phagocytic Cells ◽  
Macrophage Population ◽  
Single Cell Rna Sequencing ◽  
Visceral Adipose

scholarly journals Refining the adipose progenitor cell landscape in healthy and obese visceral adipose tissue using single-cell gene expression profiling

2019 ◽  
Vol 2 (6) ◽  
pp. e201900561 ◽  
Author(s):  
Dong Seong Cho ◽  
Bolim Lee ◽  
Jason D Doles
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Single Cell ◽  
Rna Sequencing ◽  
Visceral Adipose Tissue ◽  
Ex Vivo ◽  
Cellular Heterogeneity ◽  
Health Concern ◽  
Single Cell Rna Sequencing ◽  
Visceral Adipose

Obesity is a serious health concern and is associated with a reduced quality of life and a number of chronic diseases, including diabetes, heart disease, stroke, and cancer. With obesity rates on the rise worldwide, adipose tissue biology has become a top biomedical research priority. Despite steady growth in obesity-related research, more investigation into the basic biology of adipose tissue is needed to drive innovative solutions aiming to curtail the obesity epidemic. Adipose progenitor cells (APCs) play a central role in adipose tissue homeostasis and coordinate adipose tissue expansion and remodeling. Although APCs are well studied, defining and characterizing APC subsets remains ambiguous because of ill-defined cellular heterogeneity within this cellular compartment. In this study, we used single-cell RNA sequencing to create a cellular atlas of APC heterogeneity in mouse visceral adipose tissue. Our analysis identified two distinct populations of adipose tissue–derived stem cells (ASCs) and three distinct populations of preadipocytes (PAs). We identified novel cell surface markers that, when used in combination with traditional ASC and preadipocyte markers, could discriminate between these APC subpopulations by flow cytometry. Prospective isolation and molecular characterization of these APC subpopulations confirmed single-cell RNA sequencing gene expression signatures, and ex vivo culture revealed differential expansion/differentiation capabilities. Obese visceral adipose tissue featured relative expansion of less mature ASC and PA subpopulations, and expression analyses revealed major obesity-associated signaling alterations within each APC subpopulation. Taken together, our study highlights cellular and transcriptional heterogeneity within the APC pool, provides new tools to prospectively isolate and study these novel subpopulations, and underscores the importance of considering APC diversity when studying the etiology of obesity.

scholarly journals Sleeve gastrectomy enhances glucose utilization and remodels adipose tissue independent of weight loss

2020 ◽  
Vol 318 (5) ◽  
pp. E678-E688 ◽  
Author(s):  
David A. Harris ◽  
Amir Mina ◽  
Dimitrije Cabarkapa ◽  
Keyvan Heshmati ◽  
Renuka Subramaniam ◽  
...  
Keyword(s):  
Weight Loss ◽  
Adipose Tissue ◽  
Sleeve Gastrectomy ◽  
Glucose Uptake ◽  
Rna Sequencing ◽  
Visceral Adipose Tissue ◽  
Indirect Calorimetry ◽  
Glucose Utilization ◽  
Tissue Specific ◽  
Visceral Adipose

Sleeve gastrectomy (SG) induces weight loss-independent improvements in glucose homeostasis by unknown mechanisms. We sought to identify the metabolic adaptations responsible for these improvements. Nonobese C57BL/6J mice on standard chow underwent SG or sham surgery. Functional testing and indirect calorimetry were used to capture metabolic phenotypes. Tissue-specific glucose uptake was assessed by 18-fluorodeoxyglucose (18-FDG) PET/computed tomography, and RNA sequencing was used for gene-expression analysis. In this model, SG induced durable improvements in glucose tolerance in the absence of changes in weight, body composition, or food intake. Indirect calorimetry revealed that SG increased the average respiratory exchange ratio toward 1.0, indicating a weight-independent, systemic shift to carbohydrate utilization. Following SG, orally administered 18-FDG preferentially localized to white adipose depots, showing tissue-specific increases in glucose utilization induced by surgery. Transcriptional analysis with RNA sequencing demonstrated that increased glucose uptake in the visceral adipose tissue was associated with upregulation in transcriptional pathways involved in energy metabolism, adipocyte maturation, and adaptive and innate immune cell chemotaxis and differentiation. SG induces a rapid, weight loss-independent shift toward glucose utilization and transcriptional remodeling of metabolic and immune pathways in visceral adipose tissue. Continued study of this early post-SG physiology may lead to a better understanding of the anti-diabetic mechanisms of bariatric surgery.

scholarly journals Effects of Very Low Calorie Ketogenic Diet on the Orexinergic System, Visceral Adipose Tissue, and ROS Production

Antioxidants ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 643 ◽  
Author(s):  
Anna Valenzano ◽  
Rita Polito ◽  
Valentina Trimigno ◽  
Antonella Di Palma ◽  
Fiorenzo Moscatelli ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Cell Viability ◽  
Caloric Restriction ◽  
Visceral Adipose Tissue ◽  
Dietary Treatment ◽  
Blood Chemistry ◽  
Ros Production ◽  
Hep G2 ◽  
Orexin A ◽  
Visceral Adipose

Background: Caloric restriction is a valid strategy to reduce the visceral adipose tissue (VAT) content in obese persons. Hypocretin-1 (orexin-A) is a neuropeptide synthesized in the lateral hypothalamus that strongly modulates food intake, thus influencing adipose tissue accumulation. Therapeutic diets in obesity treatment may combine the advantages of caloric restriction and dietary ketosis. The current study aimed to evaluate the effect of a very low calorie ketogenic diet (VLCKD) in a population of obese patients. Methods: Adiposity parameters and orexin-A serum profiling were quantified over an 8 week period. The effect of the VLCKD on reactive oxygen species (ROS) production and cell viability was evaluated, in vitro, by culturing Hep-G2 cells in the presence of VLCKD sera. Results: Dietary intervention induced significant effects on body weight, adiposity, and blood chemistry parameters. Moreover, a selective reduction in VAT was measured by dual-energy X-ray absorptiometry. Orexin-A levels significantly increased after dietary treatment. Hep-G2 cell viability was not affected after 24, 48, and 72 h incubation with patients’ sera, before and after the VLCKD. In the same model system, ROS production was not significantly influenced by dietary treatment. Conclusion: The VLCKD exerts a positive effect on VAT decrease, ameliorating adiposity and blood chemistry parameters. Furthermore, short-term mild dietary ketosis does not appear to have a cytotoxic effect, nor does it represent a factor capable of increasing oxidative stress. Finally, to the best of our knowledge, this is the first study that shows an effect of the VLCKD upon the orexinergic system, supporting the usefulness of such a therapeutic intervention in promoting obesity reduction in the individual burden of this disease.

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 Neutrophils mediate the capture of peritoneal contaminants by fat-associated lymphoid clusters of the omentum

2019 ◽  
Author(s):  
Lucy H. Jackson-Jones ◽  
Peter Smith ◽  
Marlène S. Magalhaes ◽  
Jordan R. Portman ◽  
Katie J. Mylonas ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Spatial Analysis ◽  
Acute Appendicitis ◽  
Visceral Adipose Tissue ◽  
Stromal Cells ◽  
Arginine Deiminase ◽  
Protein Arginine Deiminase ◽  
Single Cell Rna Sequencing ◽  
A Site ◽  
Visceral Adipose

AbstractThe omentum is a visceral adipose tissue rich in fat-associated lymphoid clusters (FALCs), which collects peritoneal contaminants and provides a first layer of immunological defence within the abdomen. Using single-cell RNA sequencing and spatial analysis of omental stromal cells, we reveal that the surface of FALCs are covered with specialised mesothelial cells, which we name FALC cover cells. We demonstrate that CXCL1 is expressed by FALC cover cells and that CXCL1 is critical for the retention and accumulation of neutrophils within FALCs during peritonitis. We show that protein arginine deiminase 4 mediates the formation of dense neutrophil aggregates, which are required for the neutralisation of particles present in the peritoneal cavity. Finally, we provide confirmatory evidence in humans with acute appendicitis, that the omentum is also a site of neutrophil recruitment and bacterial capture, and is thus an important component of the immunological defence against the propagation of peritoneal contaminants.

scholarly journals PPARγ marks splenic precursors of multiple nonlymphoid-tissue Treg compartments

2021 ◽  
Vol 118 (13) ◽  
pp. e2025197118
Author(s):  
Chaoran Li ◽  
Andrés R. Muñoz-Rojas ◽  
Gang Wang ◽  
Alexander O. Mann ◽  
Christophe Benoist ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Single Cell ◽  
Visceral Adipose Tissue ◽  
Cell Receptor ◽  
Lymphoid Tissues ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Treg Population ◽  
Nonlymphoid Tissue ◽  
Visceral Adipose

Foxp3+CD4+ regulatory T cells (Tregs) regulate most types of immune response as well as several processes important for tissue homeostasis, for example, metabolism and repair. Dedicated Treg compartments—with distinct transcriptomes, T cell receptor repertoires, and growth/survival factor dependencies—have been identified in several nonlymphoid tissues. These Tregs are specifically adapted to function and operate in their home tissue—When, where, and how do they take on their specialized characteristics? We recently reported that a splenic Treg population expressing low levels of the transcription factor PPARγ (peroxisome proliferator-activated receptor gamma) contains precursors of Tregs residing in visceral adipose tissue. This finding made sense given that PPARγ, the “master regulator” of adipocyte differentiation, is required for the accumulation and function of Tregs in visceral adipose tissue but not in lymphoid tissues. Here we use single-cell RNA sequencing, single-cell Tcra and Tcrb sequencing, and adoptive-transfer experiments to show that, unexpectedly, the splenic PPARγlo Treg population is transcriptionally heterogeneous and engenders Tregs in multiple nonlymphoid tissues beyond visceral adipose tissue, such as skin and liver. The existence of a general pool of splenic precursors for nonlymphoid-tissue Tregs opens possibilities for regulating their emergence experimentally or therapeutically.

Sign in / Sign up

Export Citation Format

Share Document