Blog
About

0
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Higher Mast Cell Accumulation in Human Adipose Tissues Defines Clinically Favorable Obesity Sub-Phenotypes

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The identification of human obesity sub-types may improve the clinical management of patients with obesity and uncover previously unrecognized obesity mechanisms. Here, we hypothesized that adipose tissue (AT) mast cells (MC) estimation could be a mark for human obesity sub-phenotyping beyond current clinical-based stratifications, both cross-sectionally and prospectively. We estimated MC accumulation using immunohistochemistry and gene expression in abdominal visceral AT (VAT) and subcutaneous (SAT) in a human cohort of 65 persons with obesity who underwent elective abdominal (mainly bariatric) surgery, and we validated key results in two clinically similar, independent cohorts ( n = 33, n = 56). AT-MC were readily detectable by immunostaining for either c-kit or tryptase and by assessing the gene expression of KIT (KIT Proto-Oncogene, Receptor Tyrosine Kinase), TPSB2 (tryptase beta 2), and CMA1 (chymase 1). Participants were characterized as VAT-MC low if the expression of both CMA1 and TPSB2 was below the median. Higher expressers of MC genes (MC high) were metabolically healthier (lower fasting glucose and glycated hemoglobin, with higher pancreatic beta cell reserve (HOMA-β), and lower triglycerides and alkaline-phosphatase) than people with low expression (MC low). Prospectively, higher MC accumulation in VAT or SAT obtained during surgery predicted greater postoperative weight-loss response to bariatric surgery. Jointly, high AT-MC accumulation may be used to clinically define obesity sub-phenotypes, which are associated with a “healthier” cardiometabolic risk profile and a better weight-loss response to bariatric surgery.

          Related collections

          Most cited references 22

          • Record: found
          • Abstract: found
          • Article: not found

          Fibrosis and adipose tissue dysfunction.

          Fibrosis is increasingly appreciated as a major player in adipose tissue dysfunction. In rapidly expanding adipose tissue, pervasive hypoxia leads to an induction of HIF1α that in turn leads to a potent profibrotic transcriptional program. The pathophysiological impact of adipose tissue fibrosis is likely to play an equally important role on systemic metabolic alterations as fibrotic conditions play in the liver, heart, and kidney. Here, we discuss recent advances in our understanding of the genesis, modulation, and systemic impact of excessive extracellular matrix (ECM) accumulation in adipose tissue of both rodents and humans and the ensuing impact on metabolic dysfunction. Copyright © 2013 Elsevier Inc. All rights reserved.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            Fibrosis in Human Adipose Tissue: Composition, Distribution, and Link With Lipid Metabolism and Fat Mass Loss

            OBJECTIVE Fibrosis is a newly appreciated hallmark of the pathological alteration of human white adipose tissue (WAT). We investigated the composition of subcutaneous (scWAT) and omental WAT (oWAT) fibrosis in obesity and its relationship with metabolic alterations and surgery-induced weight loss. RESEARCH DESIGN AND METHODS Surgical biopsies for scWAT and oWAT were obtained in 65 obese (BMI 48.2 ± 0.8 kg/m2) and 9 lean subjects (BMI 22.8 ± 0.7 kg/m2). Obese subjects who were candidates for bariatric surgery were clinically characterized before, 3, 6, and 12 months after surgery, including fat mass evaluation by dual energy X-ray absorptiometry. WAT fibrosis was quantified and characterized using quantitative PCR, microscopic observation, and immunohistochemistry. RESULTS Fibrosis amount, distribution and collagen types (I, III, and VI) present distinct characteristics in lean and obese subjects and with WAT depots localization (subcutaneous or omental). Obese subjects had more total fibrosis in oWAT and had more pericellular fibrosis around adipocytes than lean subjects in both depots. Macrophages and mastocytes were highly represented in fibrotic bundles in oWAT, whereas scWAT was more frequently characterized by hypocellular fibrosis. The oWAT fibrosis negatively correlated with omental adipocyte diameters (R = −0.30, P = 0.02), and with triglyceride levels (R = −0.42, P < 0.01), and positively with apoA1 (R = 0.25, P = 0.05). Importantly, scWAT fibrosis correlated negatively with fat mass loss measured at the three time points after surgery. CONCLUSIONS Our data suggest differential clinical consequences of fibrosis in human WAT. In oWAT, fibrosis could contribute to limit adipocyte hypertrophy and is associated with a better lipid profile, whereas scWAT fibrosis may hamper fat mass loss induced by surgery.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis.

              There are three dominant contributors to the pathogenesis of dysfunctional adipose tissue (AT) in obesity: unresolved inflammation, inappropriate extracellular matrix (ECM) remodeling and insufficient angiogenic potential. The interactions of these processes during AT expansion reflect both a linear progression as well as feed-forward mechanisms. For example, both inflammation and inadequate angiogenic remodeling can drive fibrosis, which can in turn promote migration of immune cells into adipose depots and impede further angiogenesis. Therefore, the relationship between the members of this triad is complex but important for our understanding of the pathogenesis of obesity. Here we untangle some of these intricacies to highlight the contributions of inflammation, angiogenesis, and the ECM to both "healthy" and "unhealthy" AT expansion.
                Bookmark

                Author and article information

                Journal
                Cells
                Cells
                cells
                Cells
                MDPI
                2073-4409
                20 June 2020
                June 2020
                : 9
                : 6
                Affiliations
                [1 ]Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel; goldsnir@ 123456tauex.tau.ac.il (N.G.); beckyu@ 123456bgu.ac.il (Y.H.); pacht@ 123456post.bgu.ac.il (T.P.)
                [2 ]Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine and Sylvan Adams Sports Institute Tel Aviv University, Tel-Aviv 6997801, Israel; gepner@ 123456tauex.tau.ac.il
                [3 ]Institute of Pathology, Soroka University Medical Center Ben-Gurion University of the Negev, Beer-Sheva 84101, Israel; kezerley@ 123456bgu.ac.il (Y.K.); rsl@ 123456bgu.ac.il (R.S.-L.)
                [4 ]The Shraga Segal Department of Microbiology Immunology and Genetics Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel; gazitroi@ 123456bgu.ac.il
                [5 ]The National Institute of Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel
                [6 ]Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84101, Israel; VeraP@ 123456clalit.org.il (V.P.); iliberty@ 123456bgu.ac.il (I.F.L.); borkirsh@ 123456bgu.ac.il (B.K.)
                [7 ]Department of Medicine, University of Leipzig, 04103 Leipzig, Germany; bluma@ 123456medizin.uni-leipzig.de
                [8 ]Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig, 04103 Leipzig, Germany
                Author notes
                [* ]Correspondence: rudich@ 123456bgu.ac.il
                Article
                cells-09-01508
                10.3390/cells9061508
                7349306
                32575785
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                Categories
                Article

                Comments

                Comment on this article