Weight gain reveals dramatic increases in skeletal muscle extracellular matrix remodeling

Context: In animal models of obesity, chronic inflammation and dysregulated extracellular matrix remodeling in adipose tissue leads to insulin resistance. Whether similar pathophysiology occurs in humans is not clear. Objective: The aim of this study was to test whether 10% weight gain induced by overfeeding triggers inflammation and extracellular matrix remodeling (gene expression, protein, histology) in skeletal muscleandsc adipose tissue in humans.Wealso investigated whether such remodelingwas associated with an impaired metabolic response (hyperinsulinemic-euglycemic clamp). Design, Setting, Participants, and Intervention: Twenty-nine free-living males were fed 40% over their baseline energy requirements for 8 weeks. Results: Ten percent body weight gain prompted dramatic up-regulation of a repertoire of extracellular matrix remodeling genes in muscle and to a lesser degree in adipose tissue. The amount of extracellular matrix genes in the muscle were directly associated with the amount of lean tissue deposited during overfeeding. Despite weight gain and impaired insulin sensitivity, there was no change in local adipose tissue or systemic inflammation, but there was a slight increase in skeletal muscle inflammation. Conclusion:Wepropose that skeletal muscle extracellular matrix remodeling is another feature of the pathogenic milieu associated with energy excess and obesity, which, if disrupted, may contribute to the development of metabolic dysfunction. © 2014 by the Endocrine Society

Immunomodulatory Role of Mesenchymal Stem Cell Therapy in Vascularized Composite Allotransplantation

This review aims to summarize contemporary evidence of the in vitro and in vivo immunomodulatory effects of mesenchymal stem cells (MSCs) in promoting vascularized composite allotransplant (VCA) tolerance. An extensive literature review was performed to identify pertinent articles of merit. Prospective preclinical trials in mammal subjects receiving VCA (or skin allograft) with administration of MSCs were reviewed. Prospective clinical trials with intravascular delivery of MSCs in human populations undergoing solid organ transplant were also identified and reviewed. Sixteen preclinical studies are included. Eleven studies compared MSC monotherapy to no therapy; of these, ten reported improved graft survival, which was statistically significantly prolonged in eight. Eight studies analyzed allograft survival with MSC therapy as an adjunct to proven immunosuppressive regimens. In these studies, daily immunosuppression was transiently delivered and then stopped. In all studies, treatment-free graft survival was statistically significantly prolonged in animals that received MSC therapy. MSCs have been safely administered clinically and their use in renal transplant clinical trials provides evidence that they improve allograft transplant tolerance in clinical practice. There is potential for MSC induction therapy to overcome many of the obstacles to widespread VCA in clinical practice. Preclinical studies are needed before MSC-induced VCA tolerance becomes a clinical reality

Immunomodulatory Role of Mesenchymal Stem Cell Therapy in Vascularized Composite Allotransplantation

This review aims to summarize contemporary evidence of the in vitro and in vivo immunomodulatory effects of mesenchymal stem cells (MSCs) in promoting vascularized composite allotransplant (VCA) tolerance. An extensive literature review was performed to identify pertinent articles of merit. Prospective preclinical trials in mammal subjects receiving VCA (or skin allograft) with administration of MSCs were reviewed. Prospective clinical trials with intravascular delivery of MSCs in human populations undergoing solid organ transplant were also identified and reviewed. Sixteen preclinical studies are included. Eleven studies compared MSC monotherapy to no therapy; of these, ten reported improved graft survival, which was statistically significantly prolonged in eight. Eight studies analyzed allograft survival with MSC therapy as an adjunct to proven immunosuppressive regimens. In these studies, daily immunosuppression was transiently delivered and then stopped. In all studies, treatment-free graft survival was statistically significantly prolonged in animals that received MSC therapy. MSCs have been safely administered clinically and their use in renal transplant clinical trials provides evidence that they improve allograft transplant tolerance in clinical practice. There is potential for MSC induction therapy to overcome many of the obstacles to widespread VCA in clinical practice. Preclinical studies are needed before MSC-induced VCA tolerance becomes a clinical reality

Potential effects of aerobic exercise on the expression of perilipin 3 in the adipose tissue of women with polycystic ovary syndrome: A pilot study

© 2015 European Society of Endocrinology Printed in Great Britain. Objective: Polycystic ovary syndrome (PCOS) is associated with reduced adipose tissue lipolysis that can be rescued by aerobic exercise. We aimed to identify differences in the gene expression of perilipins and associated targets in adipose tissue in women with PCOS before and after exercise.Design and methods: We conducted a cross-sectional study in eight women with PCOS and eight women matched for BMI and age with normal cycles. Women with PCOS also completed a 16-week prospective aerobic exercise-training study. Abdominal subcutaneous adipose tissue biopsies were collected, and primary adipose-derived stromal/stem cell cultures were established from women with PCOS before 16 weeks of aerobic exercise training (nZ5) and controls (nZ5). Gene expression was measured using real-time PCR, in vitro lipolysis was measured using radiolabeled oleate, and perilipin 3 (PLIN3) protein content was measured by western blotting analysis.Results: The expression of PLIN1, PLIN3, and PLIN5, along with coatomers ARF1, ARFRP1, and βCOP was w80% lower in women with PCOS (all P\u3c0.05). Following exercise training, PLIN3 was the only perilipin to increase significantly (P\u3c0.05), along with coatomers ARF1, ARFRP1, βCOP, and SEC23A (all P\u3c0.05). Furthermore, PLIN3 protein expression was undetectable in the cell cultures from women with PCOS vs controls. Following exercise training, in vitro adipose oleate oxidation, glycerol secretion, and PLIN3 protein expression were increased, along with reductions in triglyceride content and absence of large lipid droplet morphology.Conclusions: These findings suggest that PLIN3 and coatomer GTPases are important regulators of lipolysis and triglyceride storage in the adipose tissue of women with PCOS

Potential role of increased matrix metalloproteinase-2 (MMP2) transcription in impaired adipogenesis in type 2 diabetes mellitus

We measured gene expression of paracrine regulators involved in adipocyte differentiation within the stromovascular fraction of abdominal subcutaneous adipose tissue from obese individuals with (n = 30) and without (n = 18) type 2 diabetes mellitus (T2DM). Despite similar adiposity by design, subjects with T2DM had larger adipocytes (0.92 ± 0.28 vs. 0.75 ± 0.17 μl, p < 0.05) than controls. Gene expression of the adipogenic marker aP2 was lower (0.35 ± 0.16 vs. 0.58 ± 0.27 arbitrary units, p < 0.05) whereas the expression of matricellular peptidase, MMP2 was higher (1.65 ± 0.17 vs. 1.27 ± 0.21, p = 0.02) in T2DM vs. controls. The gene expression levels between the aP2 and MMP2 were inversely correlated (r = −0.32, p = 0.03). We conclude that early steps of adipogenesis may be impaired in T2DM independently of obesity due, in part, to an upregulation of the MMP2 transcription.Severine G. Dubois, Yourka D. Tchoukalova, Leonie K. Heilbronn, Jeanine B. Albu, David E. Kelley, Steven R. Smith, Xiaobing Fang, Eric Ravussin, The Look AHEAD Adipose Research Grou

sj-docx-1-aor-10.1177_00034894231201016 – Supplemental material for Idiopathic Subglottic Stenosis Is Associated With More Frequent and Abnormal Squamous Metaplasia

Supplemental material, sj-docx-1-aor-10.1177_00034894231201016 for Idiopathic Subglottic Stenosis Is Associated With More Frequent and Abnormal Squamous Metaplasia by Yourka D. Tchoukalova, Tanya N. Phung, Maeve M. Kennedy, Danielle Miranda-Grandjean, Emanuel Becquer, Longwen Chen, Nan Zhang, Valentin Dinu, Melissa A. Wilson and David G. Lott in Annals of Otology, Rhinology & Laryngology</p