scholarly journals Advanced glycation end-products regulate extracellular matrix-adipocyte metabolic crosstalk in diabetes

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Clarissa Strieder-Barboza ◽  
Nicki A. Baker ◽  
Carmen G. Flesher ◽  
Monita Karmakar ◽  
Christopher K. Neeley ◽  
...  

AbstractThe adipose tissue extracellular matrix (ECM) regulates adipocyte cellular metabolism and is altered in obesity and type 2 diabetes, but mechanisms underlying ECM-adipocyte metabolic crosstalk are poorly defined. Advanced glycation end-product (AGE) formation is increased in diabetes. AGE alter tissue function via direct effects on ECM and by binding scavenger receptors on multiple cell types and signaling through Rho GTPases. Our goal was to determine the role and underlying mechanisms of AGE in regulating human ECM-adipocyte metabolic crosstalk. Visceral adipocytes from diabetic and non-diabetic humans with obesity were studied in 2D and 3D-ECM culture systems. AGE is increased in adipose tissue from diabetic compared to non-diabetic subjects. Glycated collagen 1 and AGE-modified ECM regulate adipocyte glucose uptake and expression of AGE scavenger receptors and Rho signaling mediators, including the DIAPH1 gene, which encodes the human Diaphanous 1 protein (hDia1). Notably, inhibition of hDia1, but not scavenger receptors RAGE or CD36, attenuated AGE-ECM inhibition of adipocyte glucose uptake. These data demonstrate that AGE-modification of ECM contributes to adipocyte insulin resistance in human diabetes, and implicate hDia1 as a potential mediator of AGE-ECM-adipocyte metabolic crosstalk.

2018 ◽  
Vol 5 (4) ◽  
pp. 91 ◽  
Author(s):  
Joris van Dongen ◽  
Martin Harmsen ◽  
Berend van der Lei ◽  
Hieronymus Stevens

The skin is the largest organ of the human body and is the first line of defense against physical and biological damage. Thus, the skin is equipped to self-repair and regenerates after trauma. Skin regeneration after damage comprises a tightly spatial-temporally regulated process of wound healing that involves virtually all cell types in the skin. Wound healing features five partially overlapping stages: homeostasis, inflammation, proliferation, re-epithelization, and finally resolution or fibrosis. Dysreguled wound healing may resolve in dermal scarring. Adipose tissue is long known for its suppressive influence on dermal scarring. Cultured adipose tissue-derived stromal cells (ASCs) secrete a plethora of regenerative growth factors and immune mediators that influence processes during wound healing e.g., angiogenesis, modulation of inflammation and extracellular matrix remodeling. In clinical practice, ASCs are usually administered as part of fractionated adipose tissue i.e., as part of enzymatically isolated SVF (cellular SVF), mechanically isolated SVF (tissue SVF), or as lipograft. Enzymatic isolation of SVF obtained adipose tissue results in suspension of adipocyte-free cells (cSVF) that lack intact intercellular adhesions or connections to extracellular matrix (ECM). Mechanical isolation of SVF from adipose tissue destructs the parenchyma (adipocytes), which results in a tissue SVF (tSVF) with intact connections between cells, as well as matrix. To date, due to a lack of well-designed prospective randomized clinical trials, neither cSVF, tSVF, whole adipose tissue, or cultured ASCs can be indicated as the preferred preparation procedure prior to therapeutic administration. In this review, we present and discuss current literature regarding the different administration options to apply ASCs (i.e., cultured ASCs, cSVF, tSVF, and lipografting) to augment dermal wound healing, as well as the available indications for clinical efficacy.


Pathogens ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1074
Author(s):  
Natalia Vacani-Martins ◽  
Marcelo Meuser-Batista ◽  
Carina de Lima Pereira dos Santos ◽  
Alejandro Marcel Hasslocher-Moreno ◽  
Andrea Henriques-Pons

Chagas disease was described more than a century ago and, despite great efforts to understand the underlying mechanisms that lead to cardiac and digestive manifestations in chronic patients, much remains to be clarified. The disease is found beyond Latin America, including Japan, the USA, France, Spain, and Australia, and is caused by the protozoan Trypanosoma cruzi. Dr. Carlos Chagas described Chagas disease in 1909 in Brazil, and hepatomegaly was among the clinical signs observed. Currently, hepatomegaly is cited in most papers published which either study acutely infected patients or experimental models, and we know that the parasite can infect multiple cell types in the liver, especially Kupffer cells and dendritic cells. Moreover, liver damage is more pronounced in cases of oral infection, which is mainly found in the Amazon region. However, the importance of liver involvement, including the hepatic immune response, in disease progression does not receive much attention. In this review, we present the very first paper published approaching the liver’s participation in the infection, as well as subsequent papers published in the last century, up to and including our recently published results. We propose that, after infection, activated peripheral T lymphocytes reach the liver and induce a shift to a pro-inflammatory ambient environment. Thus, there is an immunological integration and cooperation between peripheral and hepatic immunity, contributing to disease control.


2012 ◽  
Vol 348 (3) ◽  
pp. 559-567 ◽  
Author(s):  
Beob Soo Kim ◽  
Ji Suk Choi ◽  
Jae Dong Kim ◽  
Young Chan Choi ◽  
Yong Woo Cho

2019 ◽  
Vol 133 (22) ◽  
pp. 2329-2344 ◽  
Author(s):  
Sarah R. Anthony ◽  
Adrienne R. Guarnieri ◽  
Anamarie Gozdiff ◽  
Robert N. Helsley ◽  
Albert Phillip Owens ◽  
...  

Abstract Adipose tissue is classically recognized as the primary site of lipid storage, but in recent years has garnered appreciation for its broad role as an endocrine organ comprising multiple cell types whose collective secretome, termed as adipokines, is highly interdependent on metabolic homeostasis and inflammatory state. Anatomical location (e.g. visceral, subcutaneous, epicardial etc) and cellular composition of adipose tissue (e.g. white, beige, and brown adipocytes, macrophages etc.) also plays a critical role in determining its response to metabolic state, the resulting secretome, and its potential impact on remote tissues. Compared with other tissues, the heart has an extremely high and constant demand for energy generation, of which most is derived from oxidation of fatty acids. Availability of this fatty acid fuel source is dependent on adipose tissue, but evidence is mounting that adipose tissue plays a much broader role in cardiovascular physiology. In this review, we discuss the impact of the brown, subcutaneous, and visceral white, perivascular (PVAT), and epicardial adipose tissue (EAT) secretome on the development and progression of cardiovascular disease (CVD), with a particular focus on cardiac hypertrophy and fibrosis.


Author(s):  
Maria Veronica Lipreri ◽  
Nicola Baldini ◽  
Gabriela Graziani ◽  
Sofia Avnet

As life expectancy increases, the population experiences progressive ageing. Ageing, in turn, is connected to an increase in bone-related diseases (i.e., osteoporosis and increased risk of fractures). Hence, the search for new approaches to study the occurrence of bone-related diseases and to develop new drugs for their prevention and treatment becomes more pressing. However, to date, a reliable in vitro model that can fully recapitulate the characteristics of bone tissue, either in physiological or altered conditions, is not available. Indeed, current methods for modelling normal and pathological bone are poor predictors of treatment outcomes in humans, as they fail to mimic the in vivo cellular microenvironment and tissue complexity. Bone, in fact, is a dynamic network including differently specialized cells and the extracellular matrix, constantly subjected to external and internal stimuli. To this regard, perfused vascularized models are a novel field of investigation that can offer a new technological approach to overcome the limitations of traditional cell culture methods. It allows the combination of perfusion, mechanical and biochemical stimuli, biological cues, biomaterials (mimicking the extracellular matrix of bone), and multiple cell types. This review will discuss macro, milli, and microscale perfused devices designed to model bone structure and microenvironment, focusing on the role of perfusion and encompassing different degrees of complexity. These devices are a very first, though promising, step for the development of 3D in vitro platforms for preclinical screening of novel anabolic or anti-catabolic therapeutic approaches to improve bone health.


2021 ◽  
pp. 20-22
Author(s):  
Pradeep Kumar Radhakrishnan ◽  
Roshini Ambat ◽  
Gayathri Ananyajyothi Ambat ◽  
Bindu R Nayar ◽  
Y A Nazer

Advanced glycation end products (AGEs) are proteins or lipids that become glycated after exposure to sugars. AGEs may modify the extracellular matrix (ECM); modify the action of hormones, cytokines, and free radicals via engagement of cell surface receptors; and impact the function of intracellular proteins..AGEs block nitric oxide activity in the endothelium and cause the production of reactive oxygen species. AGEs cause microvascular and macrovascular complications by formation of cross-links between molecules in the basement membrane of the extracellular matrix and by engaging the receptor for advanced glycation end products (RAGE). Activation of RAGE by AGEs causes upregulation of the transcription factor nuclear factor-κB and its target genes. AGEs can be formed either endogenously or exogenously. Endogenously, advanced glycation takes place in all cell types via the Maillard reaction between reducing sugars and amino residues present in proteins, lipids, and DNA, resulting in loss of protein structure and function followed in some instances by cellular apoptosis. Transition to plant based antioxidant diet with traditional Indian cooking methods seems to confer multitude of health benets.


Author(s):  
Nino C Chilelli ◽  
Alessia Faggian ◽  
Francesca Favaretto ◽  
Gabriella Milan ◽  
Chiara Compagnin ◽  
...  

Glycation is one of the most important post-translational modifications in cells and tissues and gives rise to highly reactive species called advanced glycation end products (AGEs). AGEs exert their pathological effects through different ways and previous reports suggest that they may also affect adipose tissue function and insulin sensitivity. All the data belong only to short-term treatments; however, in vivo glycation is a continuous process. To fill this gap, our study investigated the effect of chronic pro-glycating conditions on adipogenesis and adipocyte's insulin responsiveness. Our results show that chronic pro-glycating treatments with methylglyoxal (MGO) and MGO modified-BSA (BSA-MGO) do not display cytotoxicity but modify gene expression without affect adipogenic differentiation. These treatments induce different levels of intracellular accumulation of AGEs which colocalize with the insulin-sensitive glucose transporter GLUT4 (solute carrier family 2 member 4- SLC2A4) in the cytoplasm; in particular, BSA-MGO reduces glucose uptake. Moreover, the adipocytes differentiated in pro-glycating conditions display an enhancement in the protein expression of the receptor for advanced glycation end products (RAGE) and glucagon-like peptide 1 receptor (GLP1R). These results suggest that intracellular AGEs could link alterations in GLP1 signaling and insulin resistance in adipose tissue, revealing that GLUT4 protein can be susceptible to glycation. Further studies are needed to clarify if this pathway could be targeted and if the reduction of AGEs accumulation in adipocytes can ameliorate insulin responsiveness.


Endocrinology ◽  
2008 ◽  
Vol 149 (10) ◽  
pp. 4794-4798 ◽  
Author(s):  
Emiko Sonoda ◽  
Shigehisa Aoki ◽  
Kazuyoshi Uchihashi ◽  
Hidenobu Soejima ◽  
Sachiko Kanaji ◽  
...  

Adipose tissue that consists of mature and immature adipocytes is suggested to contain mesenchymal stem cells (MSCs), but a culture system for analyzing their cell types within the tissue has not been established. Here we show that three-dimensional collagen gel culture of rat sc adipose tissue fragments maintained viable mature adipocytes for a long term, producing immature adipocytes and MSC-like cells from the fragments, using immunohistochemistry, ELISA, and real time RT-PCR. Bromodeoxyuridine uptake of mature adipocytes was detected. Adiponectin and leptin, and adipocyte-specific genes of adiponectin, leptin, and PPAR-γ were detected in culture assembly, whereas the lipogenesis factor insulin (20 mU/ml) and inflammation-related agent TNF-α (2 nm) increased and decreased, respectively, all of their displays. Both spindle-shaped cell types with oil red O-positive lipid droplets and those with expression of MSC markers (CD105 and CD44) developed around the fragments. The data indicate that adipose tissue-organotypic culture retains unilocular structure, proliferative ability, and some functions of mature adipocytes, generating both immature adipocytes and CD105+/CD44+ MSC-like cells. This suggests that our method will open up a new way for studying both multiple cell types within adipose tissue and the cell-based mechanisms of obesity and metabolic syndrome.


Obesity ◽  
2019 ◽  
Vol 27 (3) ◽  
pp. 399-408 ◽  
Author(s):  
Nan Wang ◽  
Ting-ting Zhao ◽  
Si-ming Li ◽  
Xu Sun ◽  
Zi-cheng Li ◽  
...  

2019 ◽  
Vol 8 (7) ◽  
pp. 917 ◽  
Author(s):  
Dinh-Toi Chu ◽  
Thuy Nguyen Thi Phuong ◽  
Nguyen Le Bao Tien ◽  
Dang Khoa Tran ◽  
Le Bui Minh ◽  
...  

Adipose tissue stem cells (ASCs), known as multipotent stem cells, are most commonly used in the clinical applications in recent years. Adipose tissues (AT) have the advantage in the harvesting, isolation, and expansion of ASCs, especially an abundant amount of stem cells compared to bone marrow. ASCs can be found in stromal vascular fractions (SVF) which are easily obtained from the dissociation of adipose tissue. Both SVFs and culture-expanded ASCs exhibit the stem cell characteristics such as differentiation into multiple cell types, regeneration, and immune regulators. Therefore, SVFs and ASCs have been researched to evaluate the safety and benefits for human use. In fact, the number of clinical trials on ASCs is going to increase by years; however, most trials are in phase I and II, and lack phase III and IV. This systemic review highlights and updates the process of the harvesting, characteristics, isolation, culture, storage, and application of ASCs, as well as provides further directions on the therapeutic use of ASCs.


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