Background: A positive energy balance promotes white adipose tissue (WAT) expansion which is characterized by activation of a repertoire of events including hypoxia, inflammation and extracellular matrix remodelling. The transmembrane glycoprotein CD248 has been implicated in all these processes in different malignant and inflammatory diseases but its potential impact in WAT and metabolic disease has not been explored.
Methods: The role of CD248 in adipocyte function and glucose metabolism was evaluated by omics analyses in human WAT, gene knockdowns in human in vitro differentiated adipocytes and by adipocyte-specific and inducible Cd248 gene knockout studies in mice.
Findings: CD248 is upregulated in white but not brown adipose tissue of obese and insulin-resistant individuals. Gene ontology analyses showed that CD248 expression associated positively with pro-inflammatory/pro-fibrotic pathways. By combining data from several human cohorts with gene knockdown experiments in human adipocytes, our results indicate that CD248 acts as a microenvironmental sensor which mediates part of the adipose tissue response to hypoxia and is specifically perturbed in white adipocytes in the obese state. Adipocyte-specific and inducible Cd248 knockouts in mice, both before and after diet-induced obesity and insulin resistance/glucose intolerance, resulted in increased microvascular density as well as attenuated hypoxia, inflammation and fibrosis without affecting fat cell volume. This was accompanied by significant improvements in insulin sensitivity and glucose tolerance.
Interpretation: CD248 exerts detrimental effects on WAT phenotype and systemic glucose homeostasis which may be reversed by suppression of adipocyte CD248. Therefore, CD248 may constitute a target to treat obesity-associated co-morbidities.
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http://dx.doi.org/10.1016/j.ebiom.2019.05.057 | DOI Listing |
Methods Mol Biol
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Department of Experimental Medicine, Biotechnology, and Molecular Biology Section, Luigi Vanvitelli Campania University, Naples, Italy.
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View Article and Find Full Text PDFGut Microbes
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Institut National de la Santé et de la Recherche Médicale (INSERM), InCOMM Intestine ClinicOralOmics Metabolism & Microbiota UMR1297 Inserm / Université Toulouse III, Toulouse, France.
Recent sets of evidence have described profiles of 16S rDNA sequences in host tissues, notably in fat pads that are significantly overrepresented and can serve as signatures of metabolic disease. However, these recent and original observations need to be further detailed and functionally defined. Here, using state-of-the-art targeted DNA sequencing and discriminant predictive approaches, we describe, from the longitudinal FLORINASH cohort of patients who underwent bariatric surgery, visceral, and subcutaneous fat pad-specific bacterial 16SrRNA signatures.
View Article and Find Full Text PDFACS Omega
December 2024
Faculty of Medicine and Health Technology, Tampere University, Arvo Ylpön katu 34, Tampere FI-33520, Finland.
While bioactive glasses (BaGs) have been studied mainly for bone applications, studies have also shown their potential for soft tissue engineering. Incorporating therapeutic ions, such as lithium (Li), strontium (Sr), and boron (B) into the BaGs, has been found to promote angiogenesis and wound healing. However, a systematic study on the impact of Li, Sr, B, and the other ions in the BaGs, has not been conducted on a wide range of cells.
View Article and Find Full Text PDFUnlabelled: Glucose transporter 4 (GLUT4) expression on white adipocytes is critical for absorbing excess blood glucose, failure of which promotes hyperglycemia. Matrix metalloproteinases (MMPs) play a crucial role in remodeling the white adipose tissue (WAT) during obesity. MMPs have multiple protein substrates, and surprisingly, it is unknown if they can directly target GLUT4 on the adipocyte surface and impair glucose absorption.
View Article and Find Full Text PDFWorld J Gastroenterol
December 2024
The Second Clinical Medical College, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China.
A recent study published in the , suggests that transplanting the gut microbiota from healthy donors can alleviate the pathological processes linked to inflammatory bowel disease (IBD), particularly Crohn's disease. In addition, that paper illustrates the effect of changes in the gut microbiota on IBD and points out that altered mesenteric adipose tissue caused by the gut microbiota and creeping fat lead to increased inflammation, which exacerbates IBD. Moreover, recent research has shown that the interaction between () and the gut microbiota is mediated through immune mechanisms, resulting in a synergistic impact on IBD.
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