Aerobic training reduces immune cell recruitment and cytokine levels in adipose tissue in obese mice

Obesity is associated with an energy imbalance that results from excessive energy intake, low diet quality, and a sedentary lifestyle. The increased consumption of a high-refined carbohydrate (HC) diet is strongly related to higher adiposity and low-grade inflammation. Aerobic training is a well-known nonpharmacological intervention to treat obesity and metabolic disturbances. However, the mechanisms through which aerobic training ameliorates the low-grade inflammation induced by an HC diet should be further investigated. Our hypothesis herein was that aerobic training would decrease the recruitment of leukocytes in adipose tissue, thereby reducing the levels of cytokines and improving metabolism in mice fed an HC diet. Male Balb/c mice were assigned to the following groups: control diet/nontrained (C-NT), control diet/trained (C-T), high-refined carbohydrate diet/nontrained (HC-NT), and high-refined carbohydrate diet/trained (HC-T). Mice were submitted to moderate-intensity training sessions that consisted of running 60 min per day for 8 weeks. An intravital microscopy technique was performed in vivo in anesthetized mice to visualize the microvasculature of the adipose tissue. The HC diet induced obesity and increased the influx of immune cells into the adipose tissue. In contrast, HC-T mice presented a lower adiposity and adipocyte area. Furthermore, relative to HC-NT mice, HC-T mice showed increased resting energy expenditure, decreased recruitment of immune cells in the adipose tissue, reduced cytokine levels, and ameliorated hyperglycemia and fatty liver deposition. Collectively, our data enhance understanding about the anti-inflammatory effect of aerobic training and shed light on the adipose tissue-mediated mechanisms by which training promotes a healthier metabolic profile.

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Adiponectin as Link Factor between Adipose Tissue and Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms20040839 ◽

2019 ◽

Vol 20 (4) ◽

pp. 839 ◽

Cited By ~ 23

Author(s):

Erika Di Zazzo ◽

Rita Polito ◽

Silvia Bartollino ◽

Ersilia Nigro ◽

Carola Porcile ◽

...

Keyword(s):

Adipose Tissue ◽

Immune Cells ◽

Active Role ◽

Low Grade ◽

Poor Clinical Outcome ◽

Different Types ◽

Obesity And Cancer ◽

Low Grade Inflammation ◽

Circulating Levels ◽

Proliferation And Invasion

Adipose tissue is a key regulator of energy balance playing an active role in lipid storage as well as in synthesizing several hormones directly involved in the pathogenesis of obesity. Obesity represents a peculiar risk factor for a growing list of cancers and is frequently associated to poor clinical outcome. The mechanism linking obesity and cancer is not completely understood, but, amongst the major players, there are both chronic low-grade inflammation and deregulation of adipokines secretion. In obesity, the adipose tissue is pervaded by an abnormal number of immune cells that create an inflammatory environment supporting tumor cell proliferation and invasion. Adiponectin (APN), the most abundant adipokine, shows anti-inflammatory, anti-proliferative and pro-apoptotic properties. Circulating levels of APN are drastically decreased in obesity, suggesting that APN may represent the link factor between obesity and cancer risk. The present review describes the recent advances on the involvement of APN and its receptors in the etiology of different types of cancer.

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Leukocyte Heterogeneity in Adipose Tissue, Including in Obesity

Circulation Research ◽

10.1161/circresaha.120.316203 ◽

2020 ◽

Vol 126 (11) ◽

pp. 1590-1612 ◽

Cited By ~ 6

Author(s):

Ada Weinstock ◽

Hernandez Moura Silva ◽

Kathryn J. Moore ◽

Ann Marie Schmidt ◽

Edward A. Fisher

Keyword(s):

Adipose Tissue ◽

Immune Cells ◽

Immune Cell ◽

Γδ T Cells ◽

The United States ◽

Low Grade ◽

Obesity Prevalence ◽

Cell Level ◽

Mortality And Morbidity ◽

Molecular Investigation

Adipose tissue (AT) plays a central role in both metabolic health and pathophysiology. Its expansion in obesity results in increased mortality and morbidity, with contributions to cardiovascular disease, diabetes mellitus, fatty liver disease, and cancer. Obesity prevalence is at an all-time high and is projected to be 50% in the United States by 2030. AT is home to a large variety of immune cells, which are critical to maintain normal tissue functions. For example, γδ T cells are fundamental for AT innervation and thermogenesis, and macrophages are required for recycling of lipids released by adipocytes. The expansion of visceral white AT promotes dysregulation of its immune cell composition and likely promotes low-grade chronic inflammation, which has been proposed to be the underlying cause for the complications of obesity. Interestingly, weight loss after obesity alters the AT immune compartment, which may account for the decreased risk of developing these complications. Recent technological advancements that allow molecular investigation on a single-cell level have led to the discovery of previously unappreciated heterogeneity in many organs and tissues. In this review, we will explore the heterogeneity of immune cells within the visceral white AT and their contributions to homeostasis and pathology.

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Adipose-on-a-chip: a dynamic microphysiological in vitro model of the human adipose for immune-metabolic analysis in type II diabetes

Lab on a Chip ◽

10.1039/c8lc00481a ◽

2019 ◽

Vol 19 (2) ◽

pp. 241-253 ◽

Cited By ~ 13

Author(s):

Yunxiao Liu ◽

Patthara Kongsuphol ◽

Su Yin Chiam ◽

Qing Xin Zhang ◽

Sajay Bhuvanendran Nair Gourikutty ◽

...

Keyword(s):

Adipose Tissue ◽

Immune Cells ◽

Type Ii Diabetes ◽

In Vitro Model ◽

Low Grade ◽

Type Ii ◽

Metabolic Analysis ◽

Vitro Model ◽

Low Grade Inflammation

Infiltration of immune cells into adipose tissue is associated with chronic low-grade inflammation in obese individuals.

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CD40 deficiency in mice exacerbates obesity-induced adipose tissue inflammation, hepatic steatosis, and insulin resistance

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00514.2012 ◽

2013 ◽

Vol 304 (9) ◽

pp. E951-E963 ◽

Cited By ~ 34

Author(s):

Chang-An Guo ◽

Sophia Kogan ◽

Shinya U. Amano ◽

Mengxi Wang ◽

Sezin Dagdeviren ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Hepatic Steatosis ◽

Immune Cell ◽

Ex Vivo ◽

Liver Steatosis ◽

Epididymal Adipose Tissue ◽

Low Grade ◽

Wild Type ◽

Cytokine Levels

The pathophysiology of obesity and type 2 diabetes in rodents and humans is characterized by low-grade inflammation in adipose tissue and liver. The CD40 receptor and its ligand CD40L initiate immune cell signaling promoting inflammation, but conflicting data on CD40L-null mice confound its role in obesity-associated insulin resistance. Here, we demonstrate that CD40 receptor-deficient mice on a high-fat diet display the expected decrease in hepatic cytokine levels but paradoxically exhibit liver steatosis, insulin resistance, and glucose intolerance compared with their age-matched wild-type controls. Hyperinsulinemic-euglycemic clamp studies also demonstrated insulin resistance in glucose utilization by the CD40-null mice compared with wild-type mice. In contrast to liver, adipose tissue in CD40-deficient animals harbors elevated cytokine levels and infiltration of inflammatory cells, particularly macrophages and CD8+effector T cells. In addition, ex vivo explants of epididymal adipose tissue from CD40−/−mice display elevated basal and isoproterenol-stimulated lipolysis, suggesting a potential increase of lipid efflux from visceral fat to the liver. These findings reveal that 1) CD40-null mice represent an unusual model of hepatic steatosis with reduced hepatic inflammation, and 2) CD40 unexpectedly functions in adipose tissue to attenuate its inflammation in obesity, thereby protecting against hepatic steatosis.

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The role of adipose tissue immune cells in obesity and low-grade inflammation

Journal of Endocrinology ◽

10.1530/joe-14-0283 ◽

2014 ◽

Vol 222 (3) ◽

pp. R113-R127 ◽

Cited By ~ 260

Author(s):

Milos Mraz ◽

Martin Haluzik

Keyword(s):

Diabetes Mellitus ◽

Adipose Tissue ◽

Immune Cells ◽

Vascular Complications ◽

Cellular Component ◽

Low Grade ◽

Induced Changes ◽

Low Grade Inflammation

Adipose tissue (AT) lies at the crossroad of nutrition, metabolism, and immunity; AT inflammation was proposed as a central mechanism connecting obesity with its metabolic and vascular complications. Resident immune cells constitute the second largest AT cellular component after adipocytes and as such play important roles in the maintenance of AT homeostasis. Obesity-induced changes in their number and activity result in the activation of local and later systemic inflammatory response, marking the transition from simple adiposity to diseases such as type 2 diabetes mellitus, arterial hypertension, and ischemic heart disease. This review has focused on the various subsets of immune cells in AT and their role in the development of AT inflammation and obesity-induced insulin resistance.

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Identification of Three Significant Genes Associated with Immune Cells Infiltration in Dysfunctional Adipose Tissue-Induced Insulin-Resistance of Obese Patients via Comprehensive Bioinformatics Analysis

International Journal of Endocrinology ◽

10.1155/2021/8820089 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Ming Zhai ◽

Peipei Luan ◽

Yefei Shi ◽

Bo Li ◽

Jianhua Kang ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Correlation Analysis ◽

Immune Cells ◽

Plasma Cells ◽

Immune Cell ◽

Low Grade ◽

Hub Genes ◽

Bioinformatics Analyses ◽

Adipose Tissue Macrophages

Background. Low-grade chronic inflammation in dysfunctional adipose tissue links obesity with insulin resistance through the activation of tissue-infiltrating immune cells. Numerous studies have reported on the pathogenesis of insulin-resistance. However, few studies focused on genes from genomic database. In this study, we would like to explore the correlation of genes and immune cells infiltration in adipose tissue via comprehensive bioinformatics analyses and experimental validation in mice and human adipose tissue. Methods. Gene Expression Omnibus (GEO) datasets (GSE27951, GSE55200, and GSE26637) of insulin-resistant individuals or type 2 diabetes patients and normal controls were downloaded to get differently expressed genes (DEGs), and GO and KEGG pathway analyses were performed. Subsequently, we integrated DEGs from three datasets and constructed commonly expressed DEGs’ PPI net-works across datasets. Center regulating module of DEGs and hub genes were screened through MCODE and cytoHubba in Cytoscape. Three most significant hub genes were further analyzed by GSEA analysis. Moreover, we verified the predicted hub genes by performing RT qPCR analysis in animals and human samples. Besides, the relative fraction of 22 immune cell types in adipose tissue was detected by using the deconvolution algorithm of CIBERSORT (Cell Type Identification by Estimating Relative Subsets of RNA Transcripts). Furthermore, based on the significantly changed types of immune cells, we performed correlation analysis between hub genes and immune cells. And, we performed immunohistochemistry and immunofluorescence analysis to verify that the hub genes were associated with adipose tissue macrophages (ATM). Results. Thirty DEGs were commonly expressed across three datasets, most of which were upregulated. DEGs mainly participated in the process of multiple immune cells’ infiltration. In protein-protein interaction network, we identified CSF1R, C1QC, and TYROBP as hub genes. GSEA analysis suggested high expression of the three hub genes was correlated with immune cells functional pathway’s activation. Immune cell infiltration and correlation analysis revealed that there were significant positive correlations between TYROBP and M0 macrophages, CSF1R and M0 macrophages, Plasma cells, and CD8 T cells. Finally, hub genes were associated with ATMs infiltration by experimental verification. Conclusions. This article revealed that CSF1R, C1QC, and TYROBP were potential hub genes associated with immune cells’ infiltration and the function of proinflammation, especially adipose tissue macrophages, in the progression of obesity-induced diabetes or insulin-resistance.

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Aerobic Training Reduces Immune Cell Recruitment and Cytokine Levels in Adipose Tissue in Obese Mice

The FASEB Journal ◽

10.1096/fasebj.2019.33.1_supplement.lb601 ◽

2019 ◽

Vol 33 (S1) ◽

Author(s):

Albená Nunes Silva ◽

Debora Romualdo Lacerda ◽

Michele Macedo Moraes ◽

Kátia Anunciação Costa ◽

Débora Fernandes Rodrigues ◽

...

Keyword(s):

Adipose Tissue ◽

Aerobic Training ◽

Immune Cell ◽

Obese Mice ◽

Cell Recruitment ◽

Cytokine Levels ◽

Immune Cell Recruitment

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Dietary Fatty Acids at the Crossroad between Obesity and Colorectal Cancer: Fine Regulators of Adipose Tissue Homeostasis and Immune Response

Cells ◽

10.3390/cells10071738 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1738

Author(s):

Manuela Del Cornò ◽

Rosaria Varì ◽

Beatrice Scazzocchio ◽

Barbara Varano ◽

Roberta Masella ◽

...

Keyword(s):

Colorectal Cancer ◽

Fatty Acids ◽

Adipose Tissue ◽

Transcription Factors ◽

Immune Cells ◽

Immune Cell ◽

Response To Therapy ◽

Dietary Fatty Acids ◽

Low Grade ◽

Cell Functions

Colorectal cancer (CRC) is among the major threatening diseases worldwide, being the third most common cancer, and a leading cause of death, with a global incidence expected to increase in the coming years. Enhanced adiposity, particularly visceral fat, is a major risk factor for the development of several tumours, including CRC, and represents an important indicator of incidence, survival, prognosis, recurrence rates, and response to therapy. The obesity-associated low-grade chronic inflammation is thought to be a key determinant in CRC development, with the adipocytes and the adipose tissue (AT) playing a significant role in the integration of diet-related endocrine, metabolic, and inflammatory signals. Furthermore, AT infiltrating immune cells contribute to local and systemic inflammation by affecting immune and cancer cell functions through the release of soluble mediators. Among the factors introduced with diet and enriched in AT, fatty acids (FA) represent major players in inflammation and are able to deeply regulate AT homeostasis and immune cell function through gene expression regulation and by modulating the activity of several transcription factors (TF). This review summarizes human studies on the effects of dietary FA on AT homeostasis and immune cell functions, highlighting the molecular pathways and TF involved. The relevance of FA balance in linking diet, AT inflammation, and CRC is also discussed. Original and review articles were searched in PubMed without temporal limitation up to March 2021, by using fatty acid as a keyword in combination with diet, obesity, colorectal cancer, inflammation, adipose tissue, immune cells, and transcription factors.

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