Matthias Blüher1, Nora Klöting, Stephan Wueest, Eugen J Schoenle, Michael R Schön, Arne Dietrich, Mathias Fasshauer, Michael Stumvoll, Daniel Konrad. 1. Department of Medicine (M.B., M.F., M.S.), University of Leipzig, 04103 Leipzig, Germany; Integriertes Forschungs-und Behandlungszentrum Obesity Diseases (N.K.), Junior Research Group Animal Models, University of Leipzig, 04103 Leipzig, Germany; Division of Pediatric Endocrinology and Diabetology and Children's Research Centre (S.W., E.J.S., D.K.), University Children's Hospital, CH-8032 Zurich, Switzerland; Städtisches Klinikum Karlsruhe (M.R.S.), Clinic of Visceral Surgery, 76133 Karlsruhe, Germany; Department of Surgery (A.D.), University of Leipzig, 04103 Leipzig, Germany; and Zurich Center for Integrative Human Physiology (D.K.), University of Zurich, CH-8006 Zurich, Switzerland.
Abstract
CONTEXT: Deletion of the death receptor Fas (CD95) in adipocytes of mice is associated with improved insulin sensitivity and reduced adipose tissue (AT) inflammation. OBJECTIVE: Here we investigate the relationship of AT Fas with human obesity. DESIGN AND METHODS: In paired samples of omental and sc AT from 256 lean and obese (including insulin-sensitive and insulin-resistant subgroups; n=60) participants, we investigated whether Fas and Fas-ligand (FasL) mRNA expression is fat depot-specific, altered in obesity, and related to measures of AT inflammation and insulin sensitivity. In addition, AT Fas mRNA expression was measured in 16 obese patients after significant weight loss of 45±6.3 kg in the context of a two-step bariatric surgery strategy. RESULTS: Fas and FasL are significantly higher expressed in omental (OM) compared to sc AT. Fas expression correlates with body mass index (OM, r2=0.44; sc, r2=0.14), AT macrophage infiltration (OM, r2=0.36; sc, r2=0.16), and glucose infusion rate in euglycemic-hyperinsulinemic clamps (OM, r2=0.17; sc, r2=0.13) (P<.05 for all). FasL expression most strongly correlates with adipocyte size (OM, r2=0.32; sc, r2=0.17) and AT macrophage infiltration (OM, r2=0.46; sc, r2=0.02). Insulin-sensitive obese individuals had significantly lower Fas and FasL expression than insulin-resistant obese individuals. Significant weight loss 12 months after gastric sleeve resection is associated with a significantly reduced Fas expression in OM and sc fat depots. CONCLUSIONS: Independently of body weight, increased Fas expression may contribute to impaired insulin sensitivity and AT dysfunction in obesity. Moreover, significant weight loss reduces Fas expression in OM and sc fat depots.
CONTEXT: Deletion of the death receptor Fas (CD95) in adipocytes of mice is associated with improved insulin sensitivity and reduced adipose tissue (AT) inflammation. OBJECTIVE: Here we investigate the relationship of AT Fas with humanobesity. DESIGN AND METHODS: In paired samples of omental and sc AT from 256 lean and obese (including insulin-sensitive and insulin-resistant subgroups; n=60) participants, we investigated whether Fas and Fas-ligand (FasL) mRNA expression is fat depot-specific, altered in obesity, and related to measures of AT inflammation and insulin sensitivity. In addition, AT Fas mRNA expression was measured in 16 obesepatients after significant weight loss of 45±6.3 kg in the context of a two-step bariatric surgery strategy. RESULTS: Fas and FasL are significantly higher expressed in omental (OM) compared to sc AT. Fas expression correlates with body mass index (OM, r2=0.44; sc, r2=0.14), AT macrophage infiltration (OM, r2=0.36; sc, r2=0.16), and glucose infusion rate in euglycemic-hyperinsulinemic clamps (OM, r2=0.17; sc, r2=0.13) (P<.05 for all). FasL expression most strongly correlates with adipocyte size (OM, r2=0.32; sc, r2=0.17) and AT macrophage infiltration (OM, r2=0.46; sc, r2=0.02). Insulin-sensitive obese individuals had significantly lower Fas and FasL expression than insulin-resistant obese individuals. Significant weight loss 12 months after gastric sleeve resection is associated with a significantly reduced Fas expression in OM and sc fat depots. CONCLUSIONS: Independently of body weight, increased Fas expression may contribute to impaired insulin sensitivity and AT dysfunction in obesity. Moreover, significant weight loss reduces Fas expression in OM and sc fat depots.
Authors: Zhanguo Gao; Jin Zhang; Tara M Henagan; Jong Han Lee; Xin Ye; Hui Wang; Jianping Ye Journal: Am J Physiol Endocrinol Metab Date: 2015-01-06 Impact factor: 4.310
Authors: Siân P Cartland; Hanis H Harith; Scott W Genner; Lei Dang; Victoria C Cogger; Melissa Vellozzi; Belinda A Di Bartolo; Shane R Thomas; Leon A Adams; Mary M Kavurma Journal: Sci Rep Date: 2017-05-15 Impact factor: 4.379
Authors: Jeu Park; Jin Young Huh; Jiyoung Oh; Jong In Kim; Sang Mun Han; Kyung Cheul Shin; Yong Geun Jeon; Sung Sik Choe; Jiyoung Park; Jae Bum Kim Journal: Genes Dev Date: 2019-11-14 Impact factor: 11.361
Authors: John Edward Farey; Oliver M Fisher; Angelique J Levert-Mignon; Patrice M Forner; Reginald V Lord Journal: Obes Surg Date: 2017-03 Impact factor: 4.129
Authors: Celestino Sardu; Gorizio Pieretti; Nunzia D'Onofrio; Feliciano Ciccarelli; Pasquale Paolisso; Maria B Passavanti; Raffaele Marfella; Michele Cioffi; Pasquale Mone; Anna M Dalise; Franca Ferraraccio; Iacopo Panarese; Antonio Gambardella; Nicola Passariello; Maria R Rizzo; Maria L Balestrieri; Gianfranco Nicoletti; Michelangela Barbieri Journal: Front Physiol Date: 2018-08-21 Impact factor: 4.566