Renin-angiotensin system inhibition reverses the altered triacylglycerol metabolic network in diabetic kidney disease
| Autor: | Subramaniam Pennathur, Felix Eichinger, Kelli M. Sas, Chih-Hong Wang, Frank C. Brosius, Thekkelnaycke M. Rajendiran, Jiahe Lin, Tanu Soni, Matthias Kretzler, Viji Nair, Hongyu Zhang, George Michailidis, Jharna Saha |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Endocrinology Diabetes and Metabolism Clinical Biochemistry Kidney Biochemistry Article Renin-Angiotensin System Mice Enos Internal medicine Diabetes mellitus Renin–angiotensin system medicine Diabetes Mellitus Animals Diabetic Nephropathies Antihypertensive Agents Triglycerides biology business.industry Lisinopril medicine.disease biology.organism_classification Endocrinology medicine.anatomical_structure Losartan lipids (amino acids peptides and proteins) business Dyslipidemia Metabolic Networks and Pathways medicine.drug Kidney disease |
| Zdroj: | Metabolomics |
| Popis: | OBJECTIVE: Dyslipidemia is a significant risk factor for progression of diabetic kidney disease (DKD). Determining the changes in individual lipids and lipid networks across a spectrum of DKD severity may identify lipids that are pathogenic to DKD progression. METHODS: We performed untargeted lipidomic analysis of kidney cortex tissue from diabetic db/db and db/db eNOS(−/−) mice along with non-diabetic littermate controls. A subset of mice were treated with the renin-angiotensin system (RAS) inhibitors, lisinopril and losartan, which improves the DKD phenotype in the db/db eNOS(−/−) mouse model. RESULTS: Of the three independent variables in this study, diabetes had the largest impact on overall lipid levels in the kidney cortex, while eNOS expression and RAS inhibition had smaller impacts on kidney lipid levels. Kidney lipid network architecture, particularly of networks involving glycerolipids such as triacylglycerols, was substantially disrupted by worsening kidney disease in the db/db eNOS(−/−) mice compared to the db/db mice, a feature that was reversed with RAS inhibition. This was associated with decreased expression of the stearoyl-CoA desaturases, Scd1 and Scd2, with RAS inhibition. CONCLUSIONS: In addition to the known salutary effect of RAS inhibition on DKD progression, our results suggest a previously unrecognized role for RAS inhibition on the kidney triacylglycerol lipid metabolic network. |
| Databáze: | OpenAIRE |
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