scholarly journals Novel insights into adipose tissue heterogeneity

Author(s):  
Tongtong Wang ◽  
Anand Kumar Sharma ◽  
Christian Wolfrum

AbstractWhen normalized to volume, adipose tissue is comprised mainly of large lipid metabolizing and storing cells called adipocytes. Strikingly, the numerical representation of non-adipocytes, composed of a wide variety of cell types found in the so-called stromal vascular fraction (SVF), outnumber adipocytes by far. Besides its function in energy storage, adipose tissue has emerged as a versatile organ that regulates systemic metabolism and has therefore constituted an attractive target for the treatment of metabolic diseases. Recent high-resolution single cells/nucleus RNA seq data exemplify an intriguingly profound diversity of both adipocytes and SVF cells in all adipose depots, and the current data, while limited, demonstrate the significance of the intra-tissue cell composition in shaping the overall functionality of this tissue. Due to the complexity of adipose tissue, our understanding of the biological relevance of this heterogeneity and plasticity is fractional. Therefore, establishing atlases of adipose tissue cell heterogeneity is the first step towards generating an understanding of these functionalities. In this review, we will describe the current knowledge on adipose tissue cell composition and the heterogeneity of single-cell RNA sequencing, including the technical limitations.

1983 ◽  
Vol 96 (6) ◽  
pp. 1689-1691
Author(s):  
U. Julius ◽  
M. Weck ◽  
W. Leonhardt ◽  
H. Schneider ◽  
K. Schollberg ◽  
...  

2021 ◽  
Vol 8 ◽  
Author(s):  
Marianthi Kalafati ◽  
Michael Lenz ◽  
Gökhan Ertaylan ◽  
Ilja C. W. Arts ◽  
Chris T. Evelo ◽  
...  

Background: Macrophages play an important role in regulating adipose tissue function, while their frequencies in adipose tissue vary between individuals. Adipose tissue infiltration by high frequencies of macrophages has been linked to changes in adipokine levels and low-grade inflammation, frequently associated with the progression of obesity. The objective of this project was to assess the contribution of relative macrophage frequencies to the overall subcutaneous adipose tissue gene expression using publicly available datasets.Methods: Seven publicly available microarray gene expression datasets from human subcutaneous adipose tissue biopsies (n = 519) were used together with TissueDecoder to determine the adipose tissue cell-type composition of each sample. We divided the subjects in four groups based on their relative macrophage frequencies. Differential gene expression analysis between the high and low relative macrophage frequencies groups was performed, adjusting for sex and study. Finally, biological processes were identified using pathway enrichment and network analysis.Results: We observed lower frequencies of adipocytes and higher frequencies of adipose stem cells in individuals characterized by high macrophage frequencies. We additionally studied whether, within subcutaneous adipose tissue, interindividual differences in the relative frequencies of macrophages were reflected in transcriptional differences in metabolic and inflammatory pathways. Adipose tissue of individuals with high macrophage frequencies had a higher expression of genes involved in complement activation, chemotaxis, focal adhesion, and oxidative stress. Similarly, we observed a lower expression of genes involved in lipid metabolism, fatty acid synthesis, and oxidation and mitochondrial respiration.Conclusion: We present an approach that combines publicly available subcutaneous adipose tissue gene expression datasets with a deconvolution algorithm to calculate subcutaneous adipose tissue cell-type composition. The results showed the expected increased inflammation gene expression profile accompanied by decreased gene expression in pathways related to lipid metabolism and mitochondrial respiration in subcutaneous adipose tissue in individuals characterized by high macrophage frequencies. This approach demonstrates the hidden strength of reusing publicly available data to gain cell-type-specific insights into adipose tissue function.


1975 ◽  
Vol 229 (2) ◽  
pp. 365-369 ◽  
Author(s):  
JC Swaner ◽  
WE Connor

After the establishment of a relatively linear decay curve for plasma [4-14C]cholesterol, rabbits were starved for 26-32 days. The plasma cholesterol concentration increased 400% during starvation. Concurrently, the plasma triglyceride level declined by 50%. While the plasma cholesterol was rising, the cholesterol specific radioactivity of the plasma remained unchanged in starved animals, but in control animals the plasma cholesterol specific radioactivity declined substantially. The cholesterol content of the liver and adipose tissue increased with starvation. The cholesterol specific radioactivities relative to plasma for adipose tissue were lower in the starved animals versus controls. These results support the hypothesis that cholesterol stored in the lipid droplet of the adipose tissue cell is released into plasma and is the chief source of the hypercholesterolemia observed during complete caloric starvation. Cholesterol metabolism in the starved animal can be depicted as a virtually closed system in both the input from biosynthesis and diet being low or zero and the output likewise being close to zero.


2017 ◽  
Vol 62 (1) ◽  
pp. 5-11 ◽  
Author(s):  
Бушманов ◽  
Andrey Bushmanov ◽  
Самойлов ◽  
Alyeksandr Samoylov ◽  
Добрынина ◽  
...  

Purpose: To investigate the effectiveness of autologous cells of stromal vascular fraction of adipose tissue in severe local radiation skin injuries after the exposure of rats to X-rays. Material and methods: Experiments were performed on Wistar rats, weighing 200–230 g. Rats were exposed locally in iliolumbar region using X-ray machine LNC-268 (RAP 100-10) at a dose of 110 Gy (30 kV tube voltage, current 6.1 mA, thick Al filter 0.1 mm), dose rate: 17.34 Gy/min. Area of the irradiation field was 8.2–8.5 cm2. Transplantation of autologous cells of stromal vascular fraction (SVFC) of adipose tissue was carried out on 21st or 35th days after irradiation. SVFC isolation was performed by means of enzymatic treatment of adipose tissue. SVFC suspension was administered subcutaneously at a dose of 1×106 cells per injection around the radiation ulcers.The severity of radiation damage to the skin and the effects of cellular therapy were evaluated in the dynamics of clinical manifestations, with the help of plane geometry and pathomorphometry. Results: It was found that by the 17–25th day after irradiation radiation ulcers were formedon rat skin. In the control group of animalsulcers persisted throughout the observation period of more than 3 months. The area of ulcers was 1,87 ± 0,35 cm2 and 1.52 ± 0.24 cm2 at 83th and 90th days after irradiation, respectively. In animals of the experimental group, with autologous stromal vascular fraction of adipose tissue, was significant decrease in ulceration the area in comparison to control animals. In 80 % of the rats treated with SVFC on 21st day after exposure, to the 90th day after irradiation complete healing of ulcers occurred with the formation of atrophic scar at the site of radiation injuries. These clinical observations and planimetric were correlated with the results of histomorphometry. Conclusion: Transplantation autologous SVFC of adipose tissue contributes to accelerate the healing of radiation ulcers after local x-ray exposure in the experiment, indicating that the prospects of using adipose tissue cell products for the treatment of severe local radiation injuries.


2000 ◽  
Vol 130 (6) ◽  
pp. 1548-1554 ◽  
Author(s):  
Michael J. Azain ◽  
Dorothy B. Hausman ◽  
Matthew B. Sisk ◽  
William P. Flatt ◽  
Dennis E. Jewell

2007 ◽  
Vol 293 (5) ◽  
pp. E1153-E1158 ◽  
Author(s):  
Hui Ren Zhou ◽  
Eun-Kyoung Kim ◽  
Hyojung Kim ◽  
Kate J. Claycombe

Studies showed that monocyte chemotactic protein-1 (MCP-1) concentrations are increased in obesity. In our current study, we demonstrate that plasma MCP-1 level in leptin-deficient ob/ob mice is significantly higher than in lean mice. Furthermore, we determined that basal adipose tissue MCP-1 mRNA levels are significantly higher in ob/ob mice compared with lean mice. To determine the mechanisms underlying obesity-associated increases in plasma and adipose tissue MCP-1 levels, we determined adipose tissue cell type sources of MCP-1 production. Our data show that adipose tissue stem cells (CD34+), macrophages (F4/80+), and stromal vascular fraction (SVF) cells express significantly higher levels of MCP-1 compared with adipocytes under both basal and lipopolysaccharide (LPS)-stimulated conditions. Furthermore, basal and LPS-induced MCP-1 secretion levels were the same for both adipose F4/80+ and CD34+ cells, whereas adipose CD34+ cells have twofold higher cell numbers (30% of total SVF cells) compared with F4/80+ macrophages (15%). Our data also show that CD34+ cells from visceral adipose tissue depots secrete significantly higher levels of MCP-1 ex vivo when compared with CD34+ cells from subcutaneous adipose tissue depots. Taken together, our data suggest that adipose CD34+ stem cells may play an important role in obesity-associated increases in plasma MCP-1 levels.


2018 ◽  
Author(s):  
Michael Lenz ◽  
Ilja C.W. Arts ◽  
Ralf L.M. Peeters ◽  
Theo M. de Kok ◽  
Gökhan Ertaylan

AbstractBackgroundHighly specialized cells work in synergy forming tissues to perform functions required for the survival of organisms. Understanding this tissue-specific cellular heterogeneity and homeostasis is essential to comprehend the development of diseases within the tissue and also for developing regenerative therapies. Cellular subpopulations in the adipose tissue have been related to disease development, but efforts towards characterizing the adipose tissue cell type composition are limited due to lack of robust cell surface markers, limited access to tissue samples, and the labor-intensive process required to identify them.ResultsWe propose a framework, identifying cellular heterogeneity while providing state-of-the-art cellular markers for each cell type present in tissues using transcriptomics level analysis. We validate our approach with an independent dataset and present the most comprehensive study of adipose tissue cell type composition to date, determining the relative amounts of 21 different cell types in 779 adipose tissue samples detailing differences across four adipose tissue depots, between genders, across ranges of BMI and in different stages of type-2 diabetes. We also highlight the heterogeneity in reported marker-based studies of adipose tissue cell type composition and provide novel cellular markers to distinguish different cell types within the adipose tissue.ConclusionsOur study provides a systematic framework for studying cell type composition in a given tissue and valuable insights into adipose tissue cell type heterogeneity in health and disease.


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