Mitrofanova A, Burke G, Merscher S, Fornoni A. New insights into renal lipid dysmetabolism in diabetic kidney disease. World J Diabetes 2021; 12(5): 524-540 [PMID: 33995842 DOI: 10.4239/wjd.v12.i5.524]
Corresponding Author of This Article
Alla Mitrofanova, PhD, Instructor, Peggy and Harold Katz Family Drug Discovery Center, University of Miami, Miller School of Medicine, 1580 NW 10th Avenue, Batchelor Bldg, 6th Floor, Miami, FL 33136, United States. a.mitrofanova@miami.edu
Research Domain of This Article
Urology & Nephrology
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Diabetes. May 15, 2021; 12(5): 524-540 Published online May 15, 2021. doi: 10.4239/wjd.v12.i5.524
New insights into renal lipid dysmetabolism in diabetic kidney disease
Alla Mitrofanova, George Burke, Sandra Merscher, Alessia Fornoni
Alla Mitrofanova, Sandra Merscher, Alessia Fornoni, Peggy and Harold Katz Family Drug Discovery Center, University of Miami, Miller School of Medicine, Miami, FL 33136, United States
Alla Mitrofanova, Sandra Merscher, Alessia Fornoni, Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami, Miller School of Medicine, Miami, FL 33136, United States
Alla Mitrofanova, George Burke, Department of Surgery, University of Miami, Miller School of Medicine, Miami, FL 33136, United States
George Burke, Diabetes Research Institute, University of Miami, Miller School of Medicine, Miami, FL 33136, United States
Author contributions: Mitrofanova A prepared the draft of the manuscript; Burke G, Merscher S and Fornoni A revised the manuscript; Merscher S helped with the figures.
Supported bythe National Institute of Health (Research in Dr. Alessia Fornoni’s laboratory), No. R01DK117599, No. R01DK104753, No. R01CA227493, No. U54DK083912, No. UM1DK100846, and No. U01DK116101; the Miami Clinical Translational Science Institute, No. UL1TR000460; and the Chernowitz Medical Research Foundation (Mitrofanova A and Burke G), No. GR016291.
Conflict-of-interest statement: Alessia Fornoni and Sandra Merscher are investors on pending or issued patents (US 10183038 and US 10052345) aimed at diagnosing or treating proteinuric kidney diseases. They stand to gain royalties from the future commercialization of these patents. Alessia Fornoni is Vice-President of L&F Health LLC and is consultant for ZyVersa Therapeutics, Inc. ZyVersa Therapeutics, Inc has licensed worldwide rights to develop and commercialize hydroxypropyl-beta-cyclodextrin from L&F Research for the treatment of kidney disease. Alessia Fornoni is the scientific founder and a shareholder of River 3 Renal Corp. Sandra Merscher is a consultant for Kintai Therapeutics, Inc and holds equity interest in L&F Research. Alessia Fornoni and Sandra Merscher are supported by Boehringer Ingelheim. G George Burke and Alla Mitrofanova declare no conflict of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Alla Mitrofanova, PhD, Instructor, Peggy and Harold Katz Family Drug Discovery Center, University of Miami, Miller School of Medicine, 1580 NW 10th Avenue, Batchelor Bldg, 6th Floor, Miami, FL 33136, United States. a.mitrofanova@miami.edu
Received: January 25, 2021 Peer-review started: January 25, 2021 First decision: February 25, 2021 Revised: March 31, 2021 Accepted: April 26, 2021 Article in press: April 26, 2021 Published online: May 15, 2021 Processing time: 100 Days and 17 Hours
Abstract
Lipid dysmetabolism is one of the main features of diabetes mellitus and manifests by dyslipidemia as well as the ectopic accumulation of lipids in various tissues and organs, including the kidney. Research suggests that impaired cholesterol metabolism, increased lipid uptake or synthesis, increased fatty acid oxidation, lipid droplet accumulation and an imbalance in biologically active sphingolipids (such as ceramide, ceramide-1-phosphate and sphingosine-1-phosphate) contribute to the development of diabetic kidney disease (DKD). Currently, the literature suggests that both quality and quantity of lipids are associated with DKD and contribute to increased reactive oxygen species production, oxidative stress, inflammation, or cell death. Therefore, control of renal lipid dysmetabolism is a very important therapeutic goal, which needs to be archived. This article will review some of the recent advances leading to a better understanding of the mechanisms of dyslipidemia and the role of particular lipids and sphingolipids in DKD.
Core Tip: The present review summarizes the recent knowledge about the role of lipids and sphingolipids in the development and progression of diabetic kidney disease (DKD). The main focus is given to the cholesterol and triglyceride metabolism abnormalities, lipid droplet accumulation and role of sphingolipids in DKD.
