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Lipidomic Analysis Reveals the Protection Mechanism of GLP-1 Analogue Dulaglutide on High-Fat Diet-Induced Chronic Kidney Disease in Mice.
Yeung, Martin Ho Yin; Leung, Ka Long; Choi, Lai Yuen; Yoo, Jung Sun; Yung, Susan; So, Pui-Kin; Wong, Chi-Ming.
Afiliación
  • Yeung MHY; Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China.
  • Leung KL; Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China.
  • Choi LY; Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China.
  • Yoo JS; Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China.
  • Yung S; Department of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
  • So PK; University Research Facility in Life Sciences, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China.
  • Wong CM; Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China.
Front Pharmacol ; 12: 777395, 2021.
Article en En | MEDLINE | ID: mdl-35299724
Many clinical studies have suggested that glucagon-like peptide-1 receptor agonists (GLP-1RAs) have renoprotective properties by ameliorating albuminuria and increasing glomerular filtration rate in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) by lowering ectopic lipid accumulation in the kidney. However, the mechanism of GLP-1RAs was hitherto unknown. Here, we conducted an unbiased lipidomic analysis using ultra-high-performance liquid chromatography/electrospray ionization-quadrupole time-of-flight mass spectrometry (UHPLC/ESI-Q-TOF-MS) and matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to reveal the changes of lipid composition and distribution in the kidneys of high-fat diet-fed mice after treatment with a long-acting GLP-1RA dulaglutide for 4 weeks. Treatment of dulaglutide dramatically improved hyperglycemia and albuminuria, but there was no substantial improvement in dyslipidemia and ectopic lipid accumulation in the kidney as compared with controls. Intriguingly, treatment of dulaglutide increases the level of an essential phospholipid constituent of inner mitochondrial membrane cardiolipin at the cortex region of the kidneys by inducing the expression of key cardiolipin biosynthesis enzymes. Previous studies demonstrated that lowered renal cardiolipin level impairs kidney function via mitochondrial damage. Our untargeted lipidomic analysis presents evidence for a new mechanism of how GLP-1RAs stimulate mitochondrial bioenergetics via increasing cardiolipin level and provides new insights into the therapeutic potential of GLP-1RAs in mitochondrial-related diseases.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Front Pharmacol Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Front Pharmacol Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza