Use of Nanovesicles from Orange Juice to Reverse Diet-Induced Gut Modifications in Diet-Induced Obese Mice

Molecular Therapy: Methods & Clinical Development

Elisabeth Errazurig-Cerda¹  Samir El-Andaloussi²  Audrey Jalabert²  Pascal Colosetti²  Dhanu Gupta²  Emmanuelle Meugnier²  Emmanuelle Berger²  Jennifer Rieusset²  Sophie Rome²  Stéphanie Chanon³  Baptiste Panthu⁴  Gilles J.P. Rautureau⁴  Oscar P.B. Wiklander⁴  Juliette Jouhet⁵  Alain Geloen⁶ 

[1] Végétale (LPCV), CNRS (UMR5168)/Université Grenoble Alpes/INRAe (UMR1417)/CEA Grenoble, Institut de Biosciences et Biotechnologies de Grenoble, France;CarMeN Laboratory (INRAe U1397, INSERM U1060, Lyon 1 University, INSA Lyon), Bâtiment CENS ELI-2D, Pierre-Bénite, France;Centre d’Imagerie Quantitative Lyon Est (CIQLE), Rockefeller Faculty of Medicine, Lyon, France;Department of Laboratory Medicine, Division of Biomolecular and Cellular Medicine, Karolinska Institutet, 141 57 Huddinge, Sweden;;Laboratoire de Physiologie Cellulaire &Université de Lyon, CNRS, Université Claude Bernard Lyon 1, ENS de Lyon, Centre de RMN à Très Hauts Champs (CRMN), FRE 2034, Villeurbanne, France;

关键词: extracellular vesicles;    lipid metabolism;    obesity;    diet-induced gut modifications;    triglycerides;    MTP;   

DOI  :  

来源: DOAJ

【 摘 要 】

We have determined whether orange juice-derived nanovesicles (ONVs) could be used for the treatment of obesity-associated intestinal complications. ONVs were characterized by lipidomic, metabolomic, electron microscopy. In vitro, intestinal barriers (IBs = Caco-2+HT-29-MTX) were treated with ONVs and co-cultured with adipocytes to monitor IB fat release. In vivo, obesity was induced with a high-fat, high-sucrose diet (HFHSD mice) for 12 weeks. Then, half of HFHSD mice were gavaged with ONVs. One-month ONV treatment did not modify HFHSD-induced insulin resistance but reversed diet-induced gut modifications. In the jejunum, ONVs increased villi size, reduced triglyceride content, and modulated mRNA levels of genes involved in immune response (tumor necrosis factor [TNF]-α and interleukin [IL]-1β), barrier permeability (CLDN1, OCLN, ZO1), fat absorption, and chylomicron release. ONVs targeted microsomal triglyceride transfer protein (MTP) and angiopoietin-like protein-4 (ANGPTL4), two therapeutic targets to reduce plasma lipids and inflammation in gastrointestinal diseases. Interestingly, ONV treatment did not aggravate liver steatosis, as MTP mRNA was increased in the liver. Therefore, ONVs protected both intestine and the liver from fat overload associated with the HFHSD. As ONVs concentrated amino acids and bioactive lipids versus orange juice, which are deficient in obese patients, the use of ONVs as a dietary supplement could bring physiological relevant compounds in the jejunum to accelerate the restoration of intestinal functions during weight loss in obese patients.

【 授权许可】

Unknown