scholarly journals Visualized macrophage dynamics and significance of S100A8 in obese fat

2015 ◽  
Vol 112 (16) ◽  
pp. E2058-E2066 ◽  
Author(s):  
Ryohei Sekimoto ◽  
Shiro Fukuda ◽  
Norikazu Maeda ◽  
Yu Tsushima ◽  
Keisuke Matsuda ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Immune Cells ◽  
Microscopic Analysis ◽  
Time Lapse ◽  
Early Event ◽  
Low Grade ◽  
Multiphoton Imaging ◽  
Inflammatory Processes

Chronic low-grade inflammation of adipose tissue plays a crucial role in the pathophysiology of obesity. Immunohistological microscopic analysis in obese fat tissue has demonstrated the infiltration of several immune cells such as macrophages, but dynamics of immune cells have not been fully elucidated and clarified. Here, by using intravital multiphoton imaging technique, to our knowledge for the first time, we analyzed and visualized the inflammatory processes in adipose tissue under high-fat and high-sucrose (HF/HS) diet with lysozyme M-EGFP transgenic (LysMEGFP) mice whose EGFP was specifically expressed in the myelomonocytic lineage. Mobility of LysMEGFP-positive macrophages was shown to be activated just 5 d after HF/HS diet, when the distinct hypertrophy of adipocytes and the accumulation of macrophages still have not become prominent. Significant increase of S100A8 was detected in mature adipocyte fraction just 5 d after HF/HS diet. Recombinant S100A8 protein stimulated chemotactic migration in vitro and in vivo, as well as induced proinflammatory molecules, both macrophages and adipocytes, such as TNF-α and chemokine (C-C motif) ligand 2. Finally, an antibody against S100A8 efficiently suppressed the HF/HS diet-induced initial inflammatory change, i.e., increased mobilization of adipose LysMEGFP-positive macrophages, and ameliorated HF/HS diet-induced insulin resistance. In conclusion, time-lapse intravital multiphoton imaging of adipose tissues identified the very early event exhibiting increased mobility of macrophages, which may be triggered by increased expression of adipose S100A8 and results in progression of chronic inflammation in situ.

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 ◽  
2019 ◽  
Vol 19 (2) ◽  
pp. 241-253 ◽  
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.

Abstract 18901: Calgranulins S100A8, S100A9 and S100A12 are Novel Genes Modified by n-3 PUFA Supplementation and Evoked Endotoxemia in Humans

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Jane F Ferguson ◽  
Chenyi Xue ◽  
Mingyao Li ◽  
Rachana Shah ◽  
Muredach P Reilly
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Low Grade ◽  
Protective Effects ◽  
Omega 3 ◽  
Healthy Individuals ◽  
Transcriptomic Response ◽  
Pufa Supplementation

Introduction: We have previously identified genes involved in the adipose transcriptomic response to evoked endotoxemia in humans. Long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) may modulate chronic low-grade systemic and adipose inflammation, conferring protection in cardiometabolic disease. However, given subtle effects of n-3 PUFA in vivo, intervention studies often lack power to detect effects on resting biomarkers. We applied unbiased transcriptomics (RNASeq) to human adipose tissue in healthy individuals following supplementation with n-3 PUFA in combination with evoked endotoxemia (LPS) as a unique genomic discovery model in n-3 PUFA modulation of inflammation. Methods: Using RNASeq we analyzed transcriptomes of adipose tissue biopsies from healthy individuals at three timepoints: before and after n-3 PUFA supplementation (n=7; 3600mg/day EPA/DHA) for 6-8 weeks compared with placebo (n=6), as well as during a subsequent evoked inflammatory challenge (LPS 0.6 ng/kg I.V.). We further explored candidate gene expression in response to n-3 PUFA and LPS using human monocytes and adipocytes in vitro. Results: The transcriptomic response to LPS was altered by n-3 PUFA supplementation. We found increased up-regulation of calgranulin genes in n-3 PUFA (S100A8 16-fold, p=0.002; S100A9 8-fold, p=0.002; S100A12 32-fold, p=0.01) compared with placebo (S100A8 2-fold, p=0.003; S100A9 1.4-fold, p=0.4; S100A12 5-fold, p=0.04). These inflammasome-activating genes may be involved in atherogenesis and inflammatory diseases, and may play a role in the recruitment of inflammatory cells to adipose tissue. We found differing calgranulin gene expression in vitro in adipocytes and monocytes after n-3 PUFA (up in monocytes, down in adipocytes post DHA p<0.001) and LPS treatment (n-3 PUFA dependent decrease in monocytes, increase in adipocytes) consistent with n-3 PUFA-dependent cell-type-specific responses to inflammatory activation. Conclusions: Unbiased transcriptomics and evoked inflammation permits enhanced genomic discovery in the context of nutritional intervention. A novel mechanism of n-3 PUFA protective effects in vivo may be through modulation of expression of calgranulin genes in response to innate immune activation.

scholarly journals Adipocyte hypertrophy is associated with lysosomal permeability both in vivo and in vitro: role in adipose tissue inflammation

2012 ◽  
Vol 303 (5) ◽  
pp. E597-E606 ◽  
Author(s):  
Agnieszka Gornicka ◽  
Jade Fettig ◽  
Akiko Eguchi ◽  
Michael P. Berk ◽  
Samjhana Thapaliya ◽  
...  
Keyword(s):  
Cell Death ◽  
Adipose Tissue ◽  
Saturated Fatty Acids ◽  
Macrophage Infiltration ◽  
Early Event ◽  
Metabolic Complications ◽  
Adipocyte Cell ◽  
Adipocyte Hypertrophy

Obesity in both humans and rodents is characterized by adipocyte hypertrophy and the presence of death adipocytes surrounded by macrophages forming “crown-like structures.” However, the biochemical pathways involved in triggering adipocyte death as well as the role of death adipocytes in adipose tissue remodeling and macrophage infiltration remain poorly understood. We now show that induction of adipocyte hypertrophy by incubation of mature adipocytes with saturated fatty acids results in lysosomal destabilization and cathepsin B (ctsb), a key lysosomal cysteine protease, activation and redistribution into the cytosol. ctsb activation was required for the lysosomal permeabilization, and its inhibition protected cells against mitochondrial dysfunction. With the use of a dietary murine model of obesity, ctsb activation was detected in adipose tissue of these mice. This is an early event during weight gain that correlates with the presence of death adipocytes, and precedes macrophage infiltration of adipose tissue. Moreover, ctsb-deficient mice showed decreased lysosomal permeabilization in adipocytes and were protected against adipocyte cell death and macrophage infiltration to adipose tissue independent of body weight. These data strongly suggest that ctsb activation and lysosomal permeabilization in adipocytes are key initial events that contribute to the adipocyte cell death and macrophage infiltration into adipose tissue associated with obesity. Inhibition of ctsb activation may be a new therapeutic strategy for the treatment of obesity-associated metabolic complications.

scholarly journals Anti-Obesity Effects of Microalgae

2019 ◽  
Vol 21 (1) ◽  
pp. 41 ◽  
Author(s):  
Saioa Gómez-Zorita ◽  
Jenifer Trepiana ◽  
Maitane González-Arceo ◽  
Leixuri Aguirre ◽  
Iñaki Milton-Laskibar ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
In Vivo Studies ◽  
Acid Oxidation ◽  
Low Grade ◽  
Food Ingredients ◽  
Brown Adipose

In recent years, microalgae have attracted great interest for their potential applications in nutraceutical and pharmaceutical industry as an interesting source of bioactive medicinal products and food ingredients with anti-oxidant, anti-inflammatory, anti-cancer, and anti-microbial properties. One potential application for bioactive microalgae compounds is obesity treatment. This review gathers together in vitro and in vivo studies which address the anti-obesity effects of microalgae extracts. The scientific literature supplies evidence supporting an anti-obesity effect of several microalgae: Euglena gracilis, Phaeodactylum tricornutum, Spirulina maxima, Spirulina platensis, or Nitzschia laevis. Regarding the mechanisms of action, microalgae can inhibit pre-adipocyte differentiation and reduce de novo lipogenesis and triglyceride (TG) assembly, thus limiting TG accumulation. Increased lipolysis and fatty acid oxidation can also be observed. Finally, microalgae can induce increased energy expenditure via thermogenesis activation in brown adipose tissue, and browning in white adipose tissue. Along with the reduction in body fat accumulation, other hallmarks of individuals with obesity, such as enhanced plasma lipid levels, insulin resistance, diabetes, or systemic low-grade inflammation are also improved by microalgae treatment. Not only the anti-obesity effect of microalgae but also the improvement of several comorbidities, previously observed in preclinical studies, has been confirmed in clinical trials.

Adipose tissue hypoxia and low-grade inflammation: a possible mechanism for ethanol-related glucose intolerance?

2015 ◽  
Vol 113 (9) ◽  
pp. 1355-1364 ◽  
Author(s):  
Zhen He ◽  
Min Li ◽  
Dongmei Zheng ◽  
Qing Chen ◽  
Wenwen Liu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glucose Tolerance ◽  
Hypoxia Inducible Factor ◽  
Ethanol Consumption ◽  
Oral Glucose ◽  
Low Grade ◽  
Tnf Α ◽  
Low Grade Inflammation

The exact mechanism of ethanol's effects on glucose tolerance has not been well determined. The present study focuses for the first time on hypoxia and low-grade inflammation in adipose tissue (AT). In the in vivo experiments, twenty-four male Wistar rats were randomly allocated into control and ethanol feeding groups. Ethanol-treated rats received edible ethanol once a day at a total dosage of 5 g/kg per d, and the controls received distilled water. Ethanol volumes were adjusted every week. At the end of 8 weeks, we carried out an oral glucose tolerance test. Blood and AT were collected for measuring hypoxia-inducible factor-1α (HIF-1α), GLUT1, TNF-α, IL-6, leptin and vascular endothelial growth factor (VEGF). In the in vitro experiments, differentiated OP9 adipocytes were incubated with 100 mm of ethanol for 48 h; the media and cells were then collected for measuring HIF-1α, GLUT1, TNF-α and IL-6. The results showed that long-term ethanol consumption impaired glucose tolerance in rats. Ethanol consumption had little influence on body weight, but both epididymal and perirenal AT were markedly enlarged in the ethanol-treated rats as compared to the controls. Visceral adipose tissue (VAT) had accumulated, and the protein levels of HIF-1α and GLUT1, the indicators of hypoxia in rat epididymal AT and OP9 adipocytes, were elevated. Secondary to the AT hypoxia, the levels of inflammation-related adipokines, such as TNF-α, IL-6, leptin and VEGF, were increased. Based on these findings, we conclude that VAT hypoxia and low-grade inflammation might be a new mechanism in the treatment of ethanol-related diabetes.

scholarly journals Exploring the Cell Stemness and the Complexity of theAdipose Tissue Niche

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1906
Author(s):  
Nadav Kislev ◽  
Roza Izgilov ◽  
Raizel Adler ◽  
Dafna Benayahu
Keyword(s):  
Adipose Tissue ◽  
Immune Cells ◽  
Inflammatory Cells ◽  
Regulatory State ◽  
Metabolic Complications ◽  
Mesenchymal Progenitors ◽  
Stem And Progenitor Cells ◽  
Combination Of Methods

Adipose tissue is a complex organ composed of different cellular populations, including mesenchymal stem and progenitor cells, adipocytes, and immune cells such as macrophages and lymphocytes. These cellular populations alter dynamically during aging or as a response to pathophysiology such as obesity. Changes in the various inflammatory cells are associated with metabolic complications and the development of insulin resistance, indicating that immune cells crosstalk with the adipocytes. Therefore, a study of the cell populations in the adipose tissue and the extracellular matrix maintaining the tissue niche is important for the knowledge on the regulatory state of the organ. We used a combination of methods to study various parameters to identify the composition of the resident cells in the adipose tissue and evaluate their profile. We analyzed the tissue structure and cells based on histology, immune fluorescence staining, and flow cytometry of cells present in the tissue in vivo and these markers’ expression in vitro. Any shift in cells’ composition influences self-renewal of the mesenchymal progenitors, and other cells affect the functionality of adipogenesis.

Ultrastructure of melanocyte-keratinocyte interactions and pigment transfer in vitro

1978 ◽  
Vol 36 (2) ◽  
pp. 650-651
Author(s):  
Raul I. Garcia ◽  
Evelyn A. Flynn ◽  
George Szabo
Keyword(s):  
Direct Injection ◽  
Skin Pigmentation ◽  
Freeze Fracture ◽  
Pigment Granule ◽  
Time Lapse ◽  
Ultrastructural Level ◽  
Lanthanum Tracer ◽  
A Cell

Skin pigmentation in mammals involves the interaction of epidermal melanocytes and keratinocytes in the structural and functional unit known as the Epidermal Melanin Unit. Melanocytes(M) synthesize melanin within specialized membrane-bound organelles, the melanosome or pigment granule. These are subsequently transferred by way of M dendrites to keratinocytes(K) by a mechanism still to be clearly defined. Three different, though not necessarily mutually exclusive, mechanisms of melanosome transfer have been proposed: cytophagocytosis by K of M dendrite tips containing melanosomes, direct injection of melanosomes into the K cytoplasm through a cell-to-cell pore or communicating channel formed by localized fusion of M and K cell membranes, release of melanosomes into the extracellular space(ECS) by exocytosis followed by K uptake using conventional phagocytosis. Variability in methods of transfer has been noted both in vivo and in vitro and there is evidence in support of each transfer mechanism. We Have previously studied M-K interactions in vitro using time-lapse cinemicrography and in vivo at the ultrastructural level using lanthanum tracer and freeze-fracture.

scholarly journals Long-Term Severe In Vitro Hypoxia Exposure Enhances the Vascularization Potential of Human Adipose Tissue-Derived Stromal Vascular Fraction Cell Engineered Tissues

2021 ◽  
Vol 22 (15) ◽  
pp. 7920
Author(s):  
Myroslava Mytsyk ◽  
Giulia Cerino ◽  
Gregory Reid ◽  
Laia Gili Sole ◽  
Friedrich S. Eckstein ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Therapeutic Potential ◽  
Stromal Vascular Fraction ◽  
Human Adipose Tissue ◽  
Bioreactor Culture ◽  
Proliferating Cells ◽  
Angiogenic Potential ◽  
Engineered Tissues

The therapeutic potential of mesenchymal stromal/stem cells (MSC) for treating cardiac ischemia strongly depends on their paracrine-mediated effects and their engraftment capacity in a hostile environment such as the infarcted myocardium. Adipose tissue-derived stromal vascular fraction (SVF) cells are a mixed population composed mainly of MSC and vascular cells, well known for their high angiogenic potential. A previous study showed that the angiogenic potential of SVF cells was further increased following their in vitro organization in an engineered tissue (patch) after perfusion-based bioreactor culture. This study aimed to investigate the possible changes in the cellular SVF composition, in vivo angiogenic potential, as well as engraftment capability upon in vitro culture in harsh hypoxia conditions. This mimics the possible delayed vascularization of the patch upon implantation in a low perfused myocardium. To this purpose, human SVF cells were seeded on a collagen sponge, cultured for 5 days in a perfusion-based bioreactor under normoxia or hypoxia (21% and <1% of oxygen tension, respectively) and subcutaneously implanted in nude rats for 3 and 28 days. Compared to ambient condition culture, hypoxic tension did not alter the SVF composition in vitro, showing similar numbers of MSC as well as endothelial and mural cells. Nevertheless, in vitro hypoxic culture significantly increased the release of vascular endothelial growth factor (p < 0.001) and the number of proliferating cells (p < 0.00001). Moreover, compared to ambient oxygen culture, exposure to hypoxia significantly enhanced the vessel length density in the engineered tissues following 28 days of implantation. The number of human cells and human proliferating cells in hypoxia-cultured constructs was also significantly increased after 3 and 28 days in vivo, compared to normoxia. These findings show that a possible in vivo delay in oxygen supply might not impair the vascularization potential of SVF- patches, which qualifies them for evaluation in a myocardial ischemia model.

scholarly journals FOXE1-Dependent Regulation of Macrophage Chemotaxis by Thyroid Cells In Vitro and In Vivo

2021 ◽  
Vol 22 (14) ◽  
pp. 7666
Author(s):  
Sara C. Credendino ◽  
Marta De Menna ◽  
Irene Cantone ◽  
Carmen Moccia ◽  
Matteo Esposito ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Immune Cells ◽  
Cancer Susceptibility ◽  
Macrophage Infiltration ◽  
M2 Macrophage ◽  
Thyroid Cells ◽  
Transcriptional Alterations ◽  
Cancer Phenotypes

Forkhead box E1 (FOXE1) is a lineage-restricted transcription factor involved in thyroid cancer susceptibility. Cancer-associated polymorphisms map in regulatory regions, thus affecting the extent of gene expression. We have recently shown that genetic reduction of FOXE1 dosage modifies multiple thyroid cancer phenotypes. To identify relevant effectors playing roles in thyroid cancer development, here we analyse FOXE1-induced transcriptional alterations in thyroid cells that do not express endogenous FOXE1. Expression of FOXE1 elicits cell migration, while transcriptome analysis reveals that several immune cells-related categories are highly enriched in differentially expressed genes, including several upregulated chemokines involved in macrophage recruitment. Accordingly, FOXE1-expressing cells induce chemotaxis of co-cultured monocytes. We then asked if FOXE1 was able to regulate macrophage infiltration in thyroid cancers in vivo by using a mouse model of cancer, either wild type or with only one functional FOXE1 allele. Expression of the same set of chemokines directly correlates with FOXE1 dosage, and pro-tumourigenic M2 macrophage infiltration is decreased in tumours with reduced FOXE1. These data establish a novel link between FOXE1 and macrophages recruitment in the thyroid cancer microenvironment, highlighting an unsuspected function of this gene in the crosstalk between neoplastic and immune cells that shape tumour development and progression.

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