Open AccessEffects of L-Carnitine Treatment on Kidney Mitochondria and Macrophages in Mice with Diabetic Nephropathy
Author(s) -
Ito Seigo,
Nakashima Masahiro,
Ishikiriyama Takuya,
Nakashima Hiroyuki,
Yamagata Akira,
Imakiire Toshihiko,
Kinoshita Manabu,
Seki Shuhji,
Kumagai Hiroo,
Oshima Naoki
Publication year - 2022
Publication title -
kidney and blood pressure research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.806
H-Index - 51
eISSN - 1423-0143
pISSN - 1420-4096
DOI - 10.1159/000522013
Subject(s) - research article
In diabetic nephropathy (DN), mitochondrial dysfunction and leakage of mitochondrial DNA (mtDNA) are caused by the downregulation of superoxide dismutase 2 (SOD2). mtDNA induces the activation of Toll-like receptor (TLR) 9, which is present in macrophages (Mφs), and triggers their activation. Methods: We orally administered L-carnitine, which exerts protective effects on the mitochondria, to obesity-induced DN (db/db) mice for 8 weeks. We then investigated the effects of L-carnitine on kidney mitochondrial reactive oxygen species (mtROS) production, circulating mtDNA content, and kidney CD11bhigh/CD11blow Mφ functions. Results: In db/db mice, mtROS production increased in proximal tubular cells and kidney CD11blow Mφs; both Mφ types showed enhanced TLR9 expression. L-Carnitine treatment suppressed mtROS production in both proximal tubular cells and CD11blow Mφs ( p < 0.01), with improved SOD2 expression in the kidney ( p < 0.01), decreased circulating mtDNA content, and reduced albuminuria. Moreover, it suppressed Mφ infiltration into kidneys and reduced TLR9 expression in Mφs ( p < 0.01), thereby lowering tumor necrosis factor-α production in CD11bhigh Mφs ( p < 0.05) and ROS production by CD11blow Mφs ( p < 0.01). Collectively, these changes alleviated DN symptoms. Conclusion: The positive effects of L-carnitine on DN suggest its potential as a novel therapeutic agent against obesity-linked DN.