Vitamin A regulates tissue-specific organ remodeling in diet-induced obesity independent of mitochondrial function

Frontiers in Endocrinology

Endocrinology

Malgorzata Szaroszyk¹  Natali Froese¹  Christian Riehle¹  Lea Naasner¹  Johann Bauersachs¹  Ivanna Shymotiuk¹  William S. Blaner²  E. Dale Abel³  Adam R. Wende⁴  Christopher Werlein⁵  Danny D. Jonigk⁶  Mark P. Kühnel⁶ 

[1] Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany;Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, United States;Department of Medicine, David Geffen School of Medicine and University of California, Los Angeles (UCLA), Health, Los Angeles, CA, United States;Division of Molecular and Cellular Pathology, Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, United States;Institute of Pathology, Hannover Medical School, Hannover, Germany;Institute of Pathology, Hannover Medical School, Hannover, Germany;Biomedical Research in End-stage and Obstructive Lung Disease Hannover (BREATH), German Lung Research Centre (DZL), Hannover, Germany;

关键词: mitochondria;    vitamin A;    diet-induced obesity;    type 2 diabetes;    liver;    kidney;    skeletal muscle;   

DOI  :  10.3389/fendo.2023.1118751

 received in 2022-12-07, accepted in 2023-02-08,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundPerturbed mitochondrial energetics and vitamin A (VitA) metabolism are associated with the pathogenesis of diet-induced obesity (DIO) and type 2 diabetes (T2D). MethodsTo test the hypothesis that VitA regulates tissue-specific mitochondrial energetics and adverse organ remodeling in DIO, we utilized a murine model of impaired VitA availability and high fat diet (HFD) feeding. Mitochondrial respiratory capacity and organ remodeling were assessed in liver, skeletal muscle, and kidney tissue, which are organs affected by T2D-associated complications and are critical for the pathogenesis of T2D. ResultsIn liver, VitA had no impact on maximal ADP-stimulated mitochondrial respiratory capacity (VADP) following HFD feeding with palmitoyl-carnitine and pyruvate each combined with malate as substrates. Interestingly, histopathological and gene expression analyses revealed that VitA mediates steatosis and adverse remodeling in DIO. In skeletal muscle, VitA did not affect VADP following HFD feeding. No morphological differences were detected between groups. In kidney, VADP was not different between groups with both combinations of substrates and VitA transduced the pro-fibrotic transcriptional response following HFD feeding.ConclusionThe present study identifies an unexpected and tissue-specific role for VitA in DIO that regulates the pro-fibrotic transcriptional response and that results in organ damage independent of changes in mitochondrial energetics.

【 授权许可】

Unknown   
Copyright © 2023 Shymotiuk, Froese, Werlein, Naasner, Szaroszyk, Kühnel, Jonigk, Blaner, Wende, Abel, Bauersachs and Riehle