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Proposal of Simplified Standardization of the Cell-Growth-Promoting Activity of Human Adipose Tissue Mesenchymal Stromal Cell Culture Supernatants

by Shin Enosawa, Sho Kobayashi and Eiji Kobayashi

Int. J. Mol. Sci. 2024, 25(10), 5197; https://doi.org/10.3390/ijms25105197 - 10 May 2024

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Abstract

The conditioned medium (CM) obtained from mesenchymal stromal cell (MSC) culture has excellent cell growth-promoting activity and is used for cosmetics and healthcare products. Unlike pharmaceuticals, strict efficacy verification is not legally required for these products. However, their efficacy must be substantiated as [...] Read more.

The conditioned medium (CM) obtained from mesenchymal stromal cell (MSC) culture has excellent cell growth-promoting activity and is used for cosmetics and healthcare products. Unlike pharmaceuticals, strict efficacy verification is not legally required for these products. However, their efficacy must be substantiated as commercial products. We attempted to simplify CM production and to standardize the evaluation of the growth-promoting activity of CM. CM was obtained through the culturing of two lines of commercially available human adipose tissue-derived MSCs using MEMα with or without 10% fetal bovine serum (FBS) for 24 h. Non-CM control media were produced by the same protocol without MSCs. Growth-promoting activities of the CM were estimated by [³H]-thymidine pulse. CM were subjected to molecular weight fractionation with ultrafiltration using 10 k-, 30 k-, 50 k-, and 100 k-membranes. The FBS-free CMs showed 1.34- to 1.85-fold increases and FBS-containing CMs showed 1.45- to 1.67-fold increases in proliferation-promoting activity compared with non-CM controls, regardless of the source of the cell. The thymidine incorporation levels were approximately three times higher in FBS-containing CMs. Aged cells also showed 1.67- to 2.48-fold increases in the activity due to FBS-containing CM, but not to FBS-free CM. The CM activities were sustained even after 1 year at 4 °C. Molecular weight fractionation showed that the activity was recovered in the fraction above 100 k. Clear and stable cell-growth-promoting activity was confirmed with CMs of commercially available adipose tissue MSCs. The activity was detected in the fraction over 100 k. We propose here the importance of standardizing the production and evaluation of CMs to indicate their specific action. Full article

(This article belongs to the Special Issue Adipose Tissue in Human Health and Disease)

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12 pages, 889 KiB

Open AccessArticle

Investigating the Role of FABP4 in Diabetes and Obesity and the Influence of Age and Ethnicity: A Comprehensive Analysis of a Cohort from the KEDP-Study

by Mohammed A. Abdalla, Jehad Abubaker, Mohamed Abu-Farha, Irina Al-Khairi, Preethi Cherian, Mohammad G. Qaddoumi, Fatema Al-Rashed, Thangavel Alphonse Thanaraj, Ahmed N. Albatineh and Fahd Al-Mulla

Int. J. Mol. Sci. 2024, 25(9), 4578; https://doi.org/10.3390/ijms25094578 - 23 Apr 2024

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Abstract

Adipocyte P2 (aP2), also known as FABP4, is an adipokine that adipose tissue produces and expresses in macrophages. Its primary role is to facilitate the transportation of fatty acids across cell membranes. Numerous studies have reported associations between FABP4 and the development of [...] Read more.

Adipocyte P2 (aP2), also known as FABP4, is an adipokine that adipose tissue produces and expresses in macrophages. Its primary role is to facilitate the transportation of fatty acids across cell membranes. Numerous studies have reported associations between FABP4 and the development of metabolic disorders. However, there is limited knowledge regarding FABP4 expression in diabetes and obesity, especially about different age groups, genders, and ethnicities. This study aims to investigate the association between FABP4 levels, diabetes mellitus, and obesity within various ethnic groups. We measured plasma FABP4 concentrations in a cohort of 2083 patients from the KDEP study and gathered anthropometric data. Additionally, we collected and analyzed clinical, biochemical, and glycemic markers using multivariate regression analysis. The average FABP4 concentration was significantly higher in female participants than in males (18.8 ng/mL vs. 14.4 ng/mL, p < 0.001, respectively), and in those over 50 years old compared to those under 50 years of age (19.3 ng/mL vs. 16.2 ng/mL, p < 0.001, respectively). In this study, significant positive associations were found between the plasma level of FABP4 and obesity markers: BMI (r = 0.496, p < 0.001), hip circumference (r = 0.463, p < 0.001), and waist circumference (WC) (r = 0.436, p < 0.001). Similar observations were also seen with glycemic markers, which included HbA1c (r = 0.126, p < 0.001), fasting blood glucose (FBG) (r = 0.184, p < 0.001), fasting insulin (r = 0.326, p < 0.001), and HOMA-IR (r = 0.333, p < 0.001). Importantly, these associations remained significant even after adjusting for age, gender, and ethnicity. Furthermore, FABP4 levels were negatively associated with male gender (β: −3.85, 95% CI: −4.92, −2.77, p < 0.001), and positively associated with age (β: 0.14, 95% CI: 0.096, 0.183, p < 0.001), BMI (β: 0.74, 95% CI: 0.644, 0.836, p < 0.001), and fasting insulin (β: 0.115, 95% CI: 0.091, 0.138, p < 0.001). In this study, plasma FABP4 levels were significantly higher in diabetic and obese participants, and they were strongly influenced by age, gender, and ethnicity. These findings suggest that FABP4 may serve as a valuable prognostic and diagnostic marker for obesity and diabetes, particularly among female patients, individuals over 50 years old, and specific ethnic groups. Full article

(This article belongs to the Special Issue Adipose Tissue in Human Health and Disease)

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15 pages, 2133 KiB

Open AccessArticle

Prognostic Impact of Visceral Adipose Tissue Imaging Parameters in Patients with Cholangiocarcinoma after Surgical Resection

by Jeong Won Lee, Ik Dong Yoo, Sun-pyo Hong, Beodeul Kang, Jung Sun Kim, Yung Kil Kim, Sang Ho Bae, Su Jin Jang and Sang Mi Lee

Int. J. Mol. Sci. 2024, 25(7), 3939; https://doi.org/10.3390/ijms25073939 - 1 Apr 2024

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Abstract

Visceral adiposity is known to be related to poor prognosis in patients with cholangiocarcinoma; however, the prognostic significance of the qualitative features of adipose tissue in cholangiocarcinoma has yet to be well defined. This study investigated the prognostic impact of adipose tissue imaging [...] Read more.

Visceral adiposity is known to be related to poor prognosis in patients with cholangiocarcinoma; however, the prognostic significance of the qualitative features of adipose tissue in cholangiocarcinoma has yet to be well defined. This study investigated the prognostic impact of adipose tissue imaging parameters reflecting the quantity and qualitative characteristics of subcutaneous (SAT) and visceral (VAT) adipose tissue on recurrence-free survival (RFS) and overall survival (OS) in 94 patients undergoing resection of cholangiocarcinoma. The area, mean computed tomography (CT) attenuation, and mean 2-deoxy-2-[¹⁸F]fluoro-D-glucose (FDG) uptake of SAT and VAT on positron emission tomography (PET)/CT for staging work-up were measured, and the relationship of these adipose tissue imaging parameters with clinicopathological factors and survival was assessed. TNM stage, histologic grade, lymphovascular invasion, and the size of cholangiocarcinoma showed positive correlations with adipose tissue imaging parameters. Multivariate survival analysis demonstrated that the visceral-to-subcutaneous adipose tissue area ratio (VSR) (p = 0.024; hazard ratio, 1.718) and mean FDG uptake of VAT (p = 0.033; hazard ratio, 9.781) were significant predictors for RFS, but all of the adipose tissue imaging parameters failed to show statistical significance for predicting OS. In addition to visceral adiposity, FDG uptake of VAT might be a promising prognostic parameter for predicting RFS in patients with cholangiocarcinoma. Full article

(This article belongs to the Special Issue Adipose Tissue in Human Health and Disease)

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18 pages, 2954 KiB

Open AccessArticle

Dexamethasone Inhibits White Adipose Tissue Browning

by Alejandra Paula Giordano, Sabrina Eliana Gambaro, Ana Alzamendi, Alejandro Ezequiel Harnichar, María Amanda Rey, Luisina Ongaro, Eduardo Spinedi, María Guillermina Zubiría and Andrés Giovambattista

Int. J. Mol. Sci. 2024, 25(5), 2714; https://doi.org/10.3390/ijms25052714 - 27 Feb 2024

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Abstract

White adipose tissue (WAT) regulates energy balance through energy storage, adipokines secretion and the thermogenesis process. Beige adipocytes are responsible for WAT thermogenesis. They are generated by adipogenesis or transdifferentiation during cold or β3-adrenergic agonist stimulus through a process called browning. Browning has [...] Read more.

White adipose tissue (WAT) regulates energy balance through energy storage, adipokines secretion and the thermogenesis process. Beige adipocytes are responsible for WAT thermogenesis. They are generated by adipogenesis or transdifferentiation during cold or β3-adrenergic agonist stimulus through a process called browning. Browning has gained significant interest for to its preventive effect on obesity. Glucocorticoids (GCs) have several functions in WAT biology; however, their role in beige adipocyte generation and WAT browning is not fully understood. The aim of our study was to determine the effect of dexamethasone (DXM) on WAT thermogenesis. For this purpose, rats were treated with DXM at room temperature (RT) or cold conditions to determine different thermogenic markers. Furthermore, the effects of DXM on the adipogenic potential of beige precursors and on mature beige adipocytes were evaluated in vitro. Our results showed that DXM decreased UCP-1 mRNA and protein levels, mainly after cold exposure. In vitro studies showed that DXM decreased the expression of a beige precursor marker (Ebf2), affecting their ability to differentiate into beige adipocytes, and inhibited the thermogenic response of mature beige adipocytes (Ucp-1, Dio2 and Pgc1α gene expressions and mitochondrial respiration). Overall, our data strongly suggest that DXM can inhibit the thermogenic program of both retroperitoneal and inguinal WAT depots, an effect that could be exerted, at least partially, by inhibiting de novo cell generation and the thermogenic response in beige adipocytes. Full article

(This article belongs to the Special Issue Adipose Tissue in Human Health and Disease)

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16 pages, 4137 KiB

Open AccessArticle

Role of Spexin in White Adipose Tissue Thermogenesis under Basal and Cold-Stimulated Conditions

by Sabrina E. Gambaro, María G. Zubiría, Alejandra P. Giordano, Patricia F. Castro, Carolina Garraza, Alejandro E. Harnichar, Ana Alzamendi, Eduardo Spinedi and Andrés Giovambattista

Int. J. Mol. Sci. 2024, 25(3), 1767; https://doi.org/10.3390/ijms25031767 - 1 Feb 2024

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Abstract

Spexin (SPX) is a novel adipokine that plays an emerging role in metabolic diseases due to its involvement in carbohydrate homeostasis, weight loss, appetite control, and gastrointestinal movement, among others. In obese patients, SPX plasma levels are reduced. Little is known about the [...] Read more.

Spexin (SPX) is a novel adipokine that plays an emerging role in metabolic diseases due to its involvement in carbohydrate homeostasis, weight loss, appetite control, and gastrointestinal movement, among others. In obese patients, SPX plasma levels are reduced. Little is known about the relationship between SPX and white adipose tissue (WAT) thermogenesis. Therefore, the aim of the present study was to evaluate the role of SPX in this process. C57BL/6J male mice were treated or not with SPX for ten days. On day 3, mice were randomly divided into two groups: one kept at room temperature and the other kept at cold temperature (4 °C). Caloric intake and body weight were recorded daily. At the end of the protocol, plasma, abdominal (epididymal), subcutaneous (inguinal), and brown AT (EAT, IAT, and BAT, respectively) depots were collected for measurements. We found that SPX treatment reduced Uncoupling protein 1 levels in WAT under both basal and cold conditions. SPX also reduced cox8b and pgc1α mRNA levels and mitochondrial DNA, principally in IAT. SPX did not modulate the number of beige precursors. SPX decreased spx levels in IAT depots and galr2 in WAT depots. No differences were observed in the BAT depots. In conclusion, we showed, for the first time, that SPX treatment in vivo reduced the thermogenic process in subcutaneous and abdominal AT, being more evident under cold stimulation. Full article

(This article belongs to the Special Issue Adipose Tissue in Human Health and Disease)

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14 pages, 1761 KiB

Open AccessArticle

Study of the Effect of Wild-Type and Transiently Expressing CXCR4 and IL-10 Mesenchymal Stromal Cells in a Mouse Model of Peritonitis

by Soledad Garcia Gómez-Heras, Mariano Garcia-Arranz, Luz Vega-Clemente, Rocio Olivera-Salazar, Juan Felipe Vélez Pinto, María Fernández-García, Héctor Guadalajara, Rosa Yáñez and Damian Garcia-Olmo

Int. J. Mol. Sci. 2024, 25(1), 520; https://doi.org/10.3390/ijms25010520 - 30 Dec 2023

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Abstract

Sepsis due to peritonitis is a process associated with an inflammatory state. Mesenchymal stromal cells (MSCs) modulate the immune system due to the paracrine factors released and may be a therapeutic alternative. Three treatment groups were developed in a murine model of peritonitis [...] Read more.

Sepsis due to peritonitis is a process associated with an inflammatory state. Mesenchymal stromal cells (MSCs) modulate the immune system due to the paracrine factors released and may be a therapeutic alternative. Three treatment groups were developed in a murine model of peritonitis to verify the effect of human adipose mesenchymal stem cell (hASCs). Additionally, a temporary modification was carried out on them to improve their arrival in inflamed tissues (CXCR4), as well as their anti-inflammatory activity (IL-10). The capacity to reduce systemic inflammation was studied using a local application (peritoneal injection) as a treatment route. Comparisons involving the therapeutic effect of wild-type ASCs and ASCs transiently expressing CXCR4 and IL-10 were carried out with the aim of generating an improved anti-inflammatory response for sepsis in addition to standard antibiotic treatment. However, under the experimental conditions used in these studies, no differences were found between both groups with ASCs. The peritoneal administration of hASCs or genetically modified hASCs constitutes an efficient and safe therapy in our model of mouse peritonitis. Full article

(This article belongs to the Special Issue Adipose Tissue in Human Health and Disease)

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16 pages, 9016 KiB

Open AccessArticle

Effects of Adipose Tissue-Specific Knockout of Delta-like Non-Canonical Notch Ligand 1 on Lipid Metabolism in Mice

by Xin Lu, Xibi Fang, Jiaqi Mi, Yue Liu, Ruimin Liu, Guanghui Li, Yue Li and Runjun Yang

Int. J. Mol. Sci. 2024, 25(1), 132; https://doi.org/10.3390/ijms25010132 - 21 Dec 2023

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Abstract

Delta-like non-canonical Notch ligand 1 (DLK1), which inhibits the differentiation of precursor adipocytes, is a recognized marker gene for precursor adipocytes. Lipids play a crucial role in energy storage and metabolism as a vital determinant of beef quality. In this study, [...] Read more.

Delta-like non-canonical Notch ligand 1 (DLK1), which inhibits the differentiation of precursor adipocytes, is a recognized marker gene for precursor adipocytes. Lipids play a crucial role in energy storage and metabolism as a vital determinant of beef quality. In this study, we investigated the mechanism of the DLK1 gene in lipid metabolism by constructing adipose tissue-specific knockout mice. We examined some phenotypic traits, including body weight, liver coefficient, fat index, the content of triglyceride (TG) and cholesterol (CHOL) in abdominal white adipose tissue (WAT) and blood. Subsequently, the fatty acid content and genes related to lipid metabolism expression were detected in DLK1^−/− and wild-type mice via GC-MS/MS analysis and quantitative real-time PCR (qRT-PCR), respectively. The results illustrated that DLK1^−/− mice exhibited significant abdominal fat deposition compared to wild-type mice. HE staining and immunohistochemistry (IHC) results showed that the white adipocytes of DLK1^−/− mice were larger, and the protein expression level of DLK1^−/− was significantly lower. Regarding the blood biochemical parameters of female mice, DLK1^−/− mice had a strikingly higher triglyceride content (p < 0.001). The fatty acid content in DLK1^−/− mice was generally reduced. There was a significant reduction in the expression levels of the majority of genes that play a crucial role in lipid metabolism. This study reveals the molecular regulatory mechanism of fat metabolism in mice and provides a molecular basis and reference for the future application of the DLK1 gene in the breeding of beef cattle with an excellent meat quality traits. It also provides a molecular basis for unravelling the complex and subtle relationship between adipose tissue and health. Full article

(This article belongs to the Special Issue Adipose Tissue in Human Health and Disease)

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18 pages, 3535 KiB

Open AccessArticle

Irisin: A Possible Marker of Adipose Tissue Dysfunction in Obesity

by Laura Tomasello, Maria Pitrone, Valentina Guarnotta, Carla Giordano and Giuseppe Pizzolanti

Int. J. Mol. Sci. 2023, 24(15), 12082; https://doi.org/10.3390/ijms241512082 - 28 Jul 2023

Cited by 1 | Viewed by 1346

Abstract

Adipose tissue (AT) secretes pro- and anti-inflammatory cytokines involved in AT homeostasis, including tumor necrosis factor-α (TNFα) and irisin. The functionality of AT is based on a regulated equilibrium between adipogenesis and extracellular matrix (ECM) remodeling. We investigated the contributions of adipose progenitors [...] Read more.

Adipose tissue (AT) secretes pro- and anti-inflammatory cytokines involved in AT homeostasis, including tumor necrosis factor-α (TNFα) and irisin. The functionality of AT is based on a regulated equilibrium between adipogenesis and extracellular matrix (ECM) remodeling. We investigated the contributions of adipose progenitors (ASCs) and adipocytes (AMCs) to TNFα-induced ECM remodeling and a possible implication of irisin in AT impairment in obesity. ASCs and AMCs were exposed to TNFα treatment and nuclear factor–kappa (NF-kB) pathway was investigated: Tissue Inhibitor of Metalloproteinase (TIMP-1), Twist Family Transcription Factor 1 (TWIST-1), and peroxisome proliferator-activated receptor-γ (PPARγ) expression levels were analyzed. The proteolytic activity of matrix metalloproteinases (MMPs) -2 and -9 was analyzed by zymography, and the irisin protein content was measured by ELISA. In inflamed AMCs, a TIMP-1/TWIST-1 imbalance leads to a drop in PPARγ. Adipogenesis and lipid storage ability impairment come with local tissue remodeling due to MMP-9 overactivation. In vitro and ex vivo measurements confirm positive correlations among inflammation, adipose secreting irisin levels, and circulating irisin levels in patients with visceral obesity. Our findings identify the NF-kB downstream effectors as molecular initiators of AT dysfunction and suggest irisin as a possible AT damage and obesity predictive factor. Full article

(This article belongs to the Special Issue Adipose Tissue in Human Health and Disease)

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17 pages, 3368 KiB

Open AccessArticle

Transcriptomic and Proteomic Analysis Reveals the Potential Role of RBMS1 in Adipogenesis and Adipocyte Metabolism

by Ghida Dairi, Saeed Al Mahri, Hicham Benabdelkamel, Assim A. Alfadda, Abdulrahman A. Alswaji, Mamoon Rashid, Shuja Shafi Malik, Jahangir Iqbal, Rizwan Ali, Maria Al Ibrahim, Khalid Al-Regaiey and Sameer Mohammad

Int. J. Mol. Sci. 2023, 24(14), 11300; https://doi.org/10.3390/ijms241411300 - 11 Jul 2023

Cited by 2 | Viewed by 1478

Abstract

Adipocytes play a critical role in maintaining a healthy systemic metabolism by storing and releasing energy in the form of fat and helping to regulate glucose and lipid levels in the body. Adipogenesis is the process through which pre-adipocytes are differentiated into mature [...] Read more.

Adipocytes play a critical role in maintaining a healthy systemic metabolism by storing and releasing energy in the form of fat and helping to regulate glucose and lipid levels in the body. Adipogenesis is the process through which pre-adipocytes are differentiated into mature adipocytes. It is a complex process involving various transcription factors and signaling pathways. The dysregulation of adipogenesis has been implicated in the development of obesity and metabolic disorders. Therefore, understanding the mechanisms that regulate adipogenesis and the factors that contribute to its dysregulation may provide insights into the prevention and treatment of these conditions. RNA-binding motif single-stranded interacting protein 1 (RBMS1) is a protein that binds to RNA and plays a critical role in various cellular processes such as alternative splicing, mRNA stability, and translation. RBMS1 polymorphism has been shown to be associated with obesity and type 2 diabetes, but the role of RBMS1 in adipose metabolism and adipogenesis is not known. We show that RBMS1 is highly expressed during the early phase of the differentiation of the murine adipocyte cell line 3T3-L1 and is significantly upregulated in the adipose tissue depots and adipocytes of high-fat-fed mice, implying a possible role in adipogenesis and adipose metabolism. Knockdown of RBMS1 in pre-adipocytes impacted the differentiation process and reduced the expression of some of the key adipogenic markers. Transcriptomic and proteomic analysis indicated that RBMS1 depletion affected the expression of several genes involved in major metabolic processes, including carbohydrate and lipid metabolism. Our findings imply that RBMS1 plays an important role in adipocyte metabolism and may offer novel therapeutic opportunity for metabolic disorders such as obesity and type 2 diabetes. Full article

(This article belongs to the Special Issue Adipose Tissue in Human Health and Disease)

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18 pages, 9977 KiB

Open AccessArticle

Extracellular Matrix Expression in Human Pancreatic Fat Cells of Patients with Normal Glucose Regulation, Prediabetes and Type 2 Diabetes

by Dorothea Siegel-Axel, Morgana Barroso Oquendo, Felicia Gerst, Falko Fend, Robert Wagner, Martin Heni, Alfred Königsrainer, Hans-Ulrich Häring, Andreas Fritsche, Erwin Schleicher, Andreas L. Birkenfeld and Norbert Stefan

Int. J. Mol. Sci. 2023, 24(13), 11169; https://doi.org/10.3390/ijms241311169 - 6 Jul 2023

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Abstract

Previously, we found that human pancreatic preadipocytes (PPAs) and islets influence each other and that the crosstalk with the fatty liver via the hepatokine fetuin-A/palmitate induces inflammatory responses. Here, we examined whether the mRNA-expression of pancreatic extracellular matrix (ECM)-forming and -degrading components differ [...] Read more.

Previously, we found that human pancreatic preadipocytes (PPAs) and islets influence each other and that the crosstalk with the fatty liver via the hepatokine fetuin-A/palmitate induces inflammatory responses. Here, we examined whether the mRNA-expression of pancreatic extracellular matrix (ECM)-forming and -degrading components differ in PPAs from individuals with normal glucose regulation (PPAs-NGR), prediabetes (PPAs-PD), and type 2 diabetes (PPAs-T2D), and whether fetuin-A/palmitate impacts ECM-formation/degradation and associated monocyte invasion. Human pancreatic resections were analyzed (immuno)histologically. PPAs were studied for mRNA expression by real-time PCR and protein secretion by Luminex analysis. Furthermore, co-cultures with human islets and monocyte migration assays in Transwell plates were conducted. We found that in comparison with NGR-PPAs, TIMP-2 mRNA levels were lower in PPAs-PD, and TGF-β1 mRNA levels were higher in PPAs-T2D. Fetuin-A/palmitate reduced fibronectin, decorin, TIMP-1/-2 and TGF-ß1 mRNA levels. Only fibronectin was strongly downregulated by fetuin-A/palmitate independently of the glycemic status. Co-culturing of PPAs with islets increased TIMP-1 mRNA expression in islets. Fetuin-A/palmitate increased MMP-1, usherin and dermatopontin mRNA-levels in co-cultured islets. A transmigration assay showed increased monocyte migration towards PPAs, which was enhanced by fetuin-A/palmitate. This was more pronounced in PPAs-T2D. The expression of distinct ECM components differs in PPAs-PD and PPAs-T2D compared to PPAs-NGR, suggesting that ECM alterations can occur even in mild hyperglycemia. Fetuin-A/palmitate impacts on ECM formation/degradation in PPAs and co-cultured islets. Fetuin-A/palmitate also enhances monocyte migration, a process which might impact on matrix turnover. Full article

(This article belongs to the Special Issue Adipose Tissue in Human Health and Disease)

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26 pages, 4851 KiB

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The Role of Epicardial Adipose Tissue in Acute Coronary Syndromes, Post-Infarct Remodeling and Cardiac Regeneration

by Kamil Krauz, Marcel Kempiński, Paweł Jańczak, Karol Momot, Maciej Zarębiński, Izabela Poprawa and Małgorzata Wojciechowska

Int. J. Mol. Sci. 2024, 25(7), 3583; https://doi.org/10.3390/ijms25073583 - 22 Mar 2024

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Abstract

Epicardial adipose tissue (EAT) is a fat deposit surrounding the heart and located under the visceral layer of the pericardium. Due to its unique features, the contribution of EAT to the pathogenesis of cardiovascular and metabolic disorders is extensively studied. Especially, EAT can [...] Read more.

Epicardial adipose tissue (EAT) is a fat deposit surrounding the heart and located under the visceral layer of the pericardium. Due to its unique features, the contribution of EAT to the pathogenesis of cardiovascular and metabolic disorders is extensively studied. Especially, EAT can be associated with the onset and development of coronary artery disease, myocardial infarction and post-infarct heart failure which all are significant problems for public health. In this article, we focus on the mechanisms of how EAT impacts acute coronary syndromes. Particular emphasis was placed on the role of inflammation and adipokines secreted by EAT. Moreover, we present how EAT affects the remodeling of the heart following myocardial infarction. We further review the role of EAT as a source of stem cells for cardiac regeneration. In addition, we describe the imaging assessment of EAT, its prognostic value, and its correlation with the clinical characteristics of patients. Full article

(This article belongs to the Special Issue Adipose Tissue in Human Health and Disease)

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14 pages, 2094 KiB

Open AccessReview

Interleukin-6: An Under-Appreciated Inducer of Thermogenic Adipocyte Differentiation

by Ádám Radványi and Tamás Röszer

Int. J. Mol. Sci. 2024, 25(5), 2810; https://doi.org/10.3390/ijms25052810 - 28 Feb 2024

Viewed by 679

Abstract

Adipose tissue inflammation is a key factor leading to obesity-associated immune disorders, such as insulin resistance, beta cell loss in the pancreatic islets, meta-inflammation, and autoimmunity. Inhibiting adipose tissue inflammation is considered a straightforward approach to abrogate these diseases. However, recent findings show [...] Read more.

Adipose tissue inflammation is a key factor leading to obesity-associated immune disorders, such as insulin resistance, beta cell loss in the pancreatic islets, meta-inflammation, and autoimmunity. Inhibiting adipose tissue inflammation is considered a straightforward approach to abrogate these diseases. However, recent findings show that certain pro-inflammatory cytokines are essential for the proper differentiation and functioning of adipocytes. Lipolysis is stimulated, and the thermogenic competence of adipocytes is unlocked by interleukin-6 (IL-6), a cytokine that was initially recognized as a key trigger of adipose tissue inflammation. Coherently, signal transducer and activator of transcription 3 (STAT3), which is a signal transducer for IL-6, is necessary for thermogenic adipocyte development. Given the impact of thermogenic adipocytes in increasing energy expenditure and reducing body adiposity, functions of IL-6 in the adipose tissue have gained attention recently. In this review, we show that IL-6 signaling may protect from excess fat accumulation by stimulating thermogenesis in adipocytes. Full article

(This article belongs to the Special Issue Adipose Tissue in Human Health and Disease)

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18 pages, 567 KiB

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Receptor for the Advanced Glycation End Products (RAGE) Pathway in Adipose Tissue Metabolism

by Klaudia Gutowska, Krzysztof Czajkowski and Alina Kuryłowicz

Int. J. Mol. Sci. 2023, 24(13), 10982; https://doi.org/10.3390/ijms241310982 - 1 Jul 2023

Cited by 7 | Viewed by 1912

Abstract

Advanced glycation end products (AGEs) are mediators in the process of cellular dysfunction in response to hyperglycemia. Numerous data indicate that the accumulation of AGEs in the extracellular matrix plays a key role in the development of obesity-related adipose tissue dysfunction. Through binding [...] Read more.

Advanced glycation end products (AGEs) are mediators in the process of cellular dysfunction in response to hyperglycemia. Numerous data indicate that the accumulation of AGEs in the extracellular matrix plays a key role in the development of obesity-related adipose tissue dysfunction. Through binding of their membrane receptor (RAGE), AGEs affect numerous intracellular pathways and impair adipocyte differentiation, metabolism, and secretory activity. Therefore, inhibiting the production and accumulation of AGEs, as well as interfering with the metabolic pathways they activate, may be a promising therapeutic strategy for restoring normal adipose tissue function and, thus, combating obesity-related comorbidities. This narrative review summarizes data on the involvement of the RAGE pathway in adipose tissue dysfunction in obesity and the development of its metabolic complications. The paper begins with a brief review of AGE synthesis and the RAGE signaling pathway. The effect of the RAGE pathway on adipose tissue development and activity is then presented. Next, data from animal and human studies on the involvement of the RAGE pathway in obesity, diabetes, and cardiovascular diseases are summarized. Finally, therapeutic perspectives based on interference with the RAGE pathway are discussed. Full article

(This article belongs to the Special Issue Adipose Tissue in Human Health and Disease)

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