scholarly journals Does C-C Motif Chemokine Ligand 2 (CCL2) Link Obesity to a Pro-Inflammatory State?

2021 ◽  
Vol 22 (3) ◽  
pp. 1500
Author(s):  
Sebastian Dommel ◽  
Matthias Blüher
Keyword(s):  
Adipose Tissue ◽  
Metabolic Diseases ◽  
Immune Cell ◽  
Current Knowledge ◽  
Low Grade ◽  
Monocyte Chemoattractant Protein 1 ◽  
Tissue Macrophage ◽  
Metabolic Inflammation ◽  
Chemokine Ligand ◽  
Chemokine Ligand 2

The mechanisms of how obesity contributes to the development of cardio-metabolic diseases are not entirely understood. Obesity is frequently associated with adipose tissue dysfunction, characterized by, e.g., adipocyte hypertrophy, ectopic fat accumulation, immune cell infiltration, and the altered secretion of adipokines. Factors secreted from adipose tissue may induce and/or maintain a local and systemic low-grade activation of the innate immune system. Attraction of macrophages into adipose tissue and altered crosstalk between macrophages, adipocytes, and other cells of adipose tissue are symptoms of metabolic inflammation. Among several secreted factors attracting immune cells to adipose tissue, chemotactic C-C motif chemokine ligand 2 (CCL2) (also described as monocyte chemoattractant protein-1 (MCP-1)) has been shown to play a crucial role in adipose tissue macrophage infiltration. In this review, we aimed to summarize and discuss the current knowledge on CCL2 with a focus on its role in linking obesity to cardio-metabolic diseases.

scholarly journals Pentraxin 3 deficiency protects from the metabolic inflammation associated to diet-induced obesity

2019 ◽  
Vol 115 (13) ◽  
pp. 1861-1872 ◽  
Author(s):  
Fabrizia Bonacina ◽  
Annalisa Moregola ◽  
Rémi Porte ◽  
Andrea Baragetti ◽  
Eduardo Bonavita ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Inflammatory Response ◽  
Immune Cell ◽  
Critical Role ◽  
Cell Phenotype ◽  
Low Grade ◽  
Pentraxin 3 ◽  
Metabolic Inflammation ◽  
Diet Induced Obesity ◽  
The Impact

Abstract Aims Low-grade chronic inflammation characterizes obesity and metabolic syndrome. Here, we aim at investigating the impact of the acute-phase protein long pentraxin 3 (PTX3) on the immune-inflammatory response occurring during diet-induced obesity. Methods and results PTX3 deficiency in mice fed a high-fat diet for 20 weeks protects from weight gain and adipose tissue deposition in visceral and subcutaneous depots. This effect is not related to changes in glucose homeostasis and lipid metabolism but is associated with an improved immune cell phenotype in the adipose tissue of Ptx3 deficient animals, which is characterized by M2-macrophages polarization and increased angiogenesis. These findings are recapitulated in humans where carriers of a PTX3 haplotype (PTX3 h2/h2 haplotype), resulting in lower PTX3 plasma levels, presented with a reduced prevalence of obesity and decreased abdominal adiposity compared with non-carriers. Conclusion Our results support a critical role for PTX3 in the onset of obesity by promoting inflammation and limiting adipose tissue vascularization and delineate PTX3 targeting as a valuable strategy for the treatment of adipose tissue-associated inflammatory response.

scholarly journals Adipocytokines in obesity and metabolic disease

2014 ◽  
Vol 220 (2) ◽  
pp. T47-T59 ◽  
Author(s):  
Haiming Cao
Keyword(s):  
Adipose Tissue ◽  
Metabolic Diseases ◽  
Therapeutic Potential ◽  
Clinical Settings ◽  
Low Grade ◽  
Endocrine Organ ◽  
Metabolic Inflammation ◽  
The Past ◽  
Wide Range ◽  
Low Grade Inflammation

The current global obesity pandemic is the leading cause for the soaring rates of metabolic diseases, especially diabetes, cardiovascular disease, hypertension, and non-alcoholic hepatosteatosis. Efforts devoted to find cures for obesity and associated disorders in the past two decades have prompted intensive interest in adipocyte biology, and have led to major advances in the mechanistic understanding of adipose tissue as an essential endocrine organ. Adipose tissue secretes an array of hormones (adipokines) that signal key organs to maintain metabolic homeostasis, and their dysfunction has been causally linked to a wide range of metabolic diseases. In addition, obesity induces production of inflammatory cytokines (often referred to together with adipokines as adipocytokines) and infiltration of immune cells into adipose tissue, which creates a state of chronic low-grade inflammation. Metabolic inflammation has been increasingly recognized as a unifying mechanism linking obesity to a broad spectrum of pathological conditions. This review focuses on classic examples of adipocytokines that have helped to form the basis of the endocrine and inflammatory roles of adipose tissue, and it also details a few newly characterized adipocytokines that provide fresh insights into adipose biology. Studies of adipocytokines in clinical settings and their therapeutic potential are also discussed.

scholarly journals Decreased TLR3 in Hyperplastic Adipose Tissue, Blood and Inflamed Adipocytes is Related to Metabolic Inflammation

2018 ◽  
Vol 51 (3) ◽  
pp. 1051-1068 ◽  
Author(s):  
Jèssica Latorre ◽  
José M. Moreno-Navarrete ◽  
Mónica Sabater ◽  
Maria Buxo ◽  
José I. Rodriguez-Hermosa ◽  
...  
Keyword(s):  
Weight Loss ◽  
Adipose Tissue ◽  
Low Grade ◽  
Metabolic Inflammation ◽  
Fat Depots ◽  
Acute Surgery ◽  
Obese Subjects ◽  
Anti Inflammatory ◽  
The Impact

Background/Aims: Obesity is characterized by the immune activation that eventually dampens insulin sensitivity and changes metabolism. This study explores the impact of different inflammatory/ anti-inflammatory paradigms on the expression of toll-like receptors (TLR) found in adipocyte cultures, adipose tissue, and blood. Methods: We evaluated by real time PCR the impact of acute surgery stress in vivo (adipose tissue) and macrophages (MCM) in vitro (adipocytes). Weight loss was chosen as an anti-inflammatory model, so TLR were analyzed in fat samples collected before and after bariatric surgery-induced weight loss. Associations with inflammatory and metabolic parameters were analyzed in non-obese and obese subjects, in parallel with gene expression measures taken in blood and isolated adipocytes/ stromal-vascular cells (SVC). Treatments with an agonist of TLR3 were conducted in human adipocyte cultures under normal conditions and upon conditions that simulated the chronic low-grade inflammatory state of obesity. Results: Surgery stress raised TLR1 and TLR8 in subcutaneous (SAT), and TLR2 in SAT and visceral (VAT) adipose tissue, while decreasing VAT TLR3 and TLR4. MCM led to increased TLR2 and diminished TLR3, TLR4, and TLR5 expressions in human adipocytes. The anti-inflammatory impact of weight loss was concomitant with decreased TLR1, TLR3, and TLR8 in SAT. Cross-sectional associations confirmed increased V/ SAT TLR1 and TLR8, and decreased TLR3 in obese patients, as compared with non-obese subjects. As expected, TLR were predominant in SVC and adipocyte precursor cells, even though expression of all of them but TLR8 (very low levels) was also found in ex vivo isolated and in vitro differentiated adipocytes. Among SVC, CD14+ macrophages showed increased TLR1, TLR2, and TLR7, but decreased TLR3 mRNA. The opposite patterns shown for TLR2 and TLR3 in V/ SAT, SVC, and inflamed adipocytes were observed in blood as well, being TLR3 more likely linked to lymphocyte instead of neutrophil counts. On the other hand, decreased TLR3 in adipocytes challenged with MCM dampened lipogenesis and the inflammatory response to Poly(I:C). Conclusion: Functional variations in the expression of TLR found in blood and hypertrophied fat depots, namely decreased TLR3 in lymphocytes and inflamed adipocytes, are linked to metabolic inflammation.

scholarly journals NLRP3 Inflammasome Activation in Adipose Tissues and Its Implications on Metabolic Diseases

2020 ◽  
Vol 21 (11) ◽  
pp. 4184 ◽  
Author(s):  
Kelvin Ka-Lok Wu ◽  
Samson Wing-Ming Cheung ◽  
Kenneth King-Yip Cheng
Keyword(s):  
Adipose Tissue ◽  
Nlrp3 Inflammasome ◽  
Metabolic Disorders ◽  
Immune Cell ◽  
Diabetic Patients ◽  
Inflammasome Activation ◽  
Low Grade ◽  
Adipose Tissues ◽  
Adipose Tissue Dysfunction ◽  
Nlrp3 Inflammasome Activation

Adipose tissue is an active endocrine and immune organ that controls systemic immunometabolism via multiple pathways. Diverse immune cell populations reside in adipose tissue, and their composition and immune responses vary with nutritional and environmental conditions. Adipose tissue dysfunction, characterized by sterile low-grade chronic inflammation and excessive immune cell infiltration, is a hallmark of obesity, as well as an important link to cardiometabolic diseases. Amongst the pro-inflammatory factors secreted by the dysfunctional adipose tissue, interleukin (IL)-1β, induced by the NLR family pyrin domain-containing 3 (NLRP3) inflammasome, not only impairs peripheral insulin sensitivity, but it also interferes with the endocrine and immune functions of adipose tissue in a paracrine manner. Human studies indicated that NLRP3 activity in adipose tissues positively correlates with obesity and its metabolic complications, and treatment with the IL-1β antibody improves glycaemia control in type 2 diabetic patients. In mouse models, genetic or pharmacological inhibition of NLRP3 activation pathways or IL-1β prevents adipose tissue dysfunction, including inflammation, fibrosis, defective lipid handling and adipogenesis, which in turn alleviates obesity and its related metabolic disorders. In this review, we summarize both the negative and positive regulators of NLRP3 inflammasome activation, and its pathophysiological consequences on immunometabolism. We also discuss the potential therapeutic approaches to targeting adipose tissue inflammasome for the treatment of obesity and its related metabolic disorders.

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

2019 ◽  
Vol 44 (5) ◽  
pp. 512-520 ◽  
Author(s):  
Débora Romualdo Lacerda ◽  
Michele Macedo Moraes ◽  
Albená Nunes-Silva ◽  
Kátia Anunciação Costa ◽  
Débora Fernandes Rodrigues ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Immune Cells ◽  
Aerobic Training ◽  
Immune Cell ◽  
Control Diet ◽  
Moderate Intensity ◽  
Low Grade ◽  
Carbohydrate Diet ◽  
Cytokine Levels ◽  
Low Grade Inflammation

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.

scholarly journals Programming effects of maternal and gestational obesity on offspring metabolism and metabolic inflammation

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
E. Chang ◽  
H. Hafner ◽  
M. Varghese ◽  
C. Griffin ◽  
J. Clemente ◽  
...  
Keyword(s):  
Body Composition ◽  
Adipose Tissue ◽  
Maternal Obesity ◽  
Immune Cell ◽  
Female Offspring ◽  
Normal Diet ◽  
Male Offspring ◽  
Reproductive Age ◽  
Metabolic Inflammation ◽  
Significant Difference

Abstract With the increasing prevalence of obesity in women of reproductive age there is a need to understand the ramifications of this on offspring. The purpose of this study is to investigate the programming effects of maternal obesity during preconception and the preconception/gestational period on adiposity and adipose tissue inflammation in offspring using an animal model. Adult female C57Bl/6J mice were assigned either normal diet, high fat diet (HFD) prior to pregnancy, or HFD prior to and through pregnancy. Some offspring were maintained on normal diet while others started HFD later in life. Offspring were assessed for body composition and metabolic responses. Lipid storing tissues were evaluated for expansion and inflammation. Male offspring from the preconception group had the greatest weight gain, most subcutaneous adipose tissue, and largest liver mass when introduced to postnatal HFD. Male offspring of the preconception/gestation group had worsened glucose tolerance and an increase in resident (CD11c−) adipose tissue macrophages (ATMs) when exposed to postnatal HFD. Female offspring had no significant difference in any parameter between the diet treatment groups. In conclusion, this study demonstrates that prenatal and pregnancy windows have independent programming effects on offspring. Preconception exposure affects body composition and adiposity while gestation exposure affects metabolism and tissue immune cell phenotypes.

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