Treatment of tubular damage in high-fat-diet-fed obese mice using sodium-glucose co-transporter inhibitors.

Autor: Saitoh S; Department of Biomedical Molecular Sciences (Anatomy II), Fujita Health University School of Medicine, Toyoake, Japan., Takaki T; Department of Anatomy, Showa University School of Medicine, Tokyo, Japan.; Center for Electron microscopy, Showa University School of Medicine, Tokyo, Japan., Nakajima K; Center for Joint Research Facilities Support, Research Promotion and Support Headquarters, Fujita Health University, Toyoake, Japan.; Institute for Glyco-core Research (iGCORE), Gifu University, Gifu, Japan., Wo B; Department of Anatomy and Molecular Histology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Japan.; Department of Histology and Embryology, Medical College of Chifeng University, Chifeng, China., Terashima H; JEOL Ltd., Akishima, Japan., Shimo S; Department of Occupational Therapy, Health Science University, Fujikawaguchiko, Japan., Nguyen HB; Division of Neurobiology and Bioinformatics, National Institute for Physiological Sciences, Okazaki, Japan.; Department of Anatomy and Structural Biology, Graduate School of Medical Science, University of Yamanashi, Chuo, Japan.; Department of Anatomy, Faculty of Medicine, University of Medicine and Pharmacy (UMP), Ho Chi Minh, Vietnam., Thai TQ; Division of Neurobiology and Bioinformatics, National Institute for Physiological Sciences, Okazaki, Japan.; Department of Anatomy and Structural Biology, Graduate School of Medical Science, University of Yamanashi, Chuo, Japan.; Department of Histology Embryology Genetics, Faculty of Basic Medical Sciences, Pham Ngoc Thach University of Medicine, Ho Chi Minh, Vietnam., Kumamoto K; Education and Research Facility of Animal Models for Human Diseases, Fujita Health University, Toyoake, Japan., Kunisawa K; Department of Regulatory Science for Evaluation & Development of Pharmaceuticals & Devices, Fujita Health University Graduate School of Health Sciences, Toyoake, Japan., Nagao S; Education and Research Facility of Animal Models for Human Diseases, Fujita Health University, Toyoake, Japan., Tojo A; Division of Nephrology & Hypertension, Dokkyo Medical University, Mibu, Japan., Ohno N; Division of Ultrastructural Research, National Institute of Physiological Sciences, Okazaki, Japan.; Department of Anatomy, Division of Histology and Cell Biology, Jichi Medical University, Shimotsuke, Japan., Takahashi K; Department of Biomedical Molecular Sciences (Anatomy II), Fujita Health University School of Medicine, Toyoake, Japan.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2023 Feb 13; Vol. 18 (2), pp. e0281770. Date of Electronic Publication: 2023 Feb 13 (Print Publication: 2023).
DOI: 10.1371/journal.pone.0281770
Abstrakt: A long-term high-fat diet (HFD) causes obesity and changes in renal lipid metabolism and lysosomal dysfunction in mice, causing renal damage. Sodium-glucose co-transporter inhibitors, including phlorizin, exert nephroprotective effects in patients with chronic kidney disease, but the underlying mechanism remains unclear. A HFD or standard diet was fed to adult C57BL/6J male mice, and phlorizin was administered. Lamellar body components of the proximal tubular epithelial cells (PTECs) were investigated. After phlorizin administration in HFD-fed mice, sphingomyelin and ceramide in urine and tissues were assessed and label-free quantitative proteomics was performed using kidney tissue samples. Mitochondrial elongation by fusion was effective in the PTECs of HFD-fed obese mice under phlorizin administration, and many lamellar bodies were found in the apical portion of the S2 segment of the proximal tubule. Phlorizin functioned as a diuretic, releasing lamellar bodies from the apical membrane of PTECs and clearing the obstruction in nephrons. The main component of the lamellar bodies was sphingomyelin. On the first day of phlorizin administration in HFD-fed obese mice, the diuretic effect was increased, and more sphingomyelin was excreted through urine than in vehicle-treated mice. The expressions of three peroxisomal β-oxidation proteins involved in fatty acid metabolism were downregulated after phlorizin administration in the kidneys of HFD-fed mice. Fatty acid elongation protein levels increased with phlorizin administration, indicating an increase in long-chain fatty acids. Lamellar bodies accumulated in the proximal renal tubule of the S2 segment of the HFD-fed mice, indicating that the urinary excretion of lamellar bodies has nephroprotective effects.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2023 Saitoh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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