OBJECTIVE: Pathogenic immunoglobulins are produced during the development of obesity and contribute to the development of insulin resistance (IR). However, the mechanisms by which these antibodies affect IR are largely unknown. This study investigated whether Fc-receptors contribute to the development of diet-induced obesity and IR by studying FcRγ(-/-) mice that lack the γ-subunit necessary for signaling and cell surface expression of FcγR and FcεRI. METHODS: FcRγ(-/-) and wild-type (WT) mice were fed a high-fat diet (HFD) to induce obesity. At 4 and 11 weeks, body weight and insulin sensitivity were measured, and adipose tissue (AT) inflammation was determined. Furthermore, intestinal triglyceride (TG) uptake and plasma TG clearance were determined, and gut microbiota composition was analyzed. RESULTS: FcRγ(-/-) mice gained less weight after 11 weeks of HFD. They had reduced adiposity, adipose tissue inflammation, and IR. Interestingly, FcRγ(-/-) mice had higher lean mass compared to WT mice, which was associated with increased energy expenditure. Intestinal TG absorption was increased whereas plasma TG clearance was not affected in FcRγ(-/-) mice. Gut microbial composition differed significantly and might therefore have added to the observed phenotype. CONCLUSIONS: FcRγ-chain deficiency reduces the development of diet-induced obesity, as well as associated AT inflammation and IR at 11 weeks of HFD.
OBJECTIVE: Pathogenic immunoglobulins are produced during the development of obesity and contribute to the development of insulin resistance (IR). However, the mechanisms by which these antibodies affect IR are largely unknown. This study investigated whether Fc-receptors contribute to the development of diet-induced obesity and IR by studying FcRγ(-/-) mice that lack the γ-subunit necessary for signaling and cell surface expression of FcγR and FcεRI. METHODS: FcRγ(-/-) and wild-type (WT) mice were fed a high-fat diet (HFD) to induce obesity. At 4 and 11 weeks, body weight and insulin sensitivity were measured, and adipose tissue (AT) inflammation was determined. Furthermore, intestinal triglyceride (TG) uptake and plasma TG clearance were determined, and gut microbiota composition was analyzed. RESULTS: FcRγ(-/-) mice gained less weight after 11 weeks of HFD. They had reduced adiposity, adipose tissue inflammation, and IR. Interestingly, FcRγ(-/-) mice had higher lean mass compared to WT mice, which was associated with increased energy expenditure. Intestinal TG absorption was increased whereas plasma TG clearance was not affected in FcRγ(-/-) mice. Gut microbial composition differed significantly and might therefore have added to the observed phenotype. CONCLUSIONS: FcRγ-chain deficiency reduces the development of diet-induced obesity, as well as associated AT inflammation and IR at 11 weeks of HFD.
Authors: A D van Dam; L van Beek; A C M Pronk; S M van den Berg; J Van den Bossche; M P J de Winther; F Koning; C van Kooten; P C N Rensen; M R Boon; J S Verbeek; K Willems van Dijk; V van Harmelen Journal: Int J Obes (Lond) Date: 2017-08-30 Impact factor: 5.095
Authors: Marieke F Fransen; Hreinn Benonisson; Wendy W van Maren; Heng Sheng Sow; Cor Breukel; Margot M Linssen; Jill W C Claassens; Conny Brouwers; Jos van der Kaa; Marcel Camps; Jan Willem Kleinovink; Kelly K Vonk; Sandra van Heiningen; Ngaisah Klar; Lianne van Beek; Vanessa van Harmelen; Lucia Daxinger; Kutty S Nandakumar; Rikard Holmdahl; Chris Coward; Qingshun Lin; Sachiko Hirose; Daniela Salvatori; Thorbald van Hall; Cees van Kooten; Piero Mastroeni; Ferry Ossendorp; J Sjef Verbeek Journal: J Immunol Date: 2018-03-09 Impact factor: 5.422
Authors: Saeed Katiraei; Lisa R Hoving; Lianne van Beek; Sharida Mohamedhoesein; Françoise Carlotti; Janna A van Diepen; Patrick C N Rensen; Mihai G Netea; Ko Willems van Dijk; Jimmy F P Berbée; Vanessa van Harmelen Journal: PLoS One Date: 2017-04-26 Impact factor: 3.240
Authors: Iván Arias-de la Rosa; Alejandro Escudero-Contreras; Miriam Ruiz-Ponce; Laura Cuesta-López; Cristóbal Román-Rodríguez; Carlos Pérez-Sánchez; Patricia Ruiz-Limón; Rocío Guzman- Ruiz; Fernando Leiva-Cepas; Juan Alcaide; Pedro Segui; Chamaida Plasencia; Ana Martinez-Feito; Pilar Font; María C Ábalos; Rafaela Ortega; María M Malagón; Francisco J Tinahones; Eduardo Collantes-Estévez; Chary López-Pedrera; Nuria Barbarroja Journal: iScience Date: 2022-08-06