Altered renal hemodynamics is associated with glomerular lipid accumulation in obese Dahl salt-sensitive leptin receptor mutant rats
| Autor: | Alyssa Nichols, Bibek Poudel, Kasi C McPherson, Cassandra Stubbs, Lateia Taylor, Michael R. Garrett, Jan M. Williams, Ashley C. Johnson, Denise C. Cornelius, Corbin A. Shields |
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| Rok vydání: | 2020 |
| Předmět: |
CD36 Antigens
medicine.medical_specialty Lipid accumulation Physiology Mutant Kidney Glomerulus Renal function urologic and male genital diseases Renal Circulation Internal medicine medicine Animals Renal hemodynamics Genetic Predisposition to Disease Obesity Sodium Chloride Dietary Adiposity Dahl salt sensitive Leptin receptor Rats Inbred Dahl Strain (chemistry) Chemistry Hemodynamics Chemokine CXCL16 medicine.disease Lipid Metabolism Disease Models Animal Proteinuria Endocrinology Phenotype Adipose Tissue Hypertension Mutation Receptors Leptin ATP-Binding Cassette Transporters Kidney Diseases ATP Binding Cassette Transporter 1 Glomerular Filtration Rate Research Article |
| Zdroj: | Am J Physiol Renal Physiol |
| ISSN: | 1522-1466 |
| Popis: | The present study examined whether development of renal injury in the nondiabetic obese Dahl salt-sensitive leptin receptor mutant (SSLepRmutant) strain is associated with elevations in glomerular filtration rate and renal lipid accumulation. Baseline mean arterial pressure at 6 wk of age was similar between Dahl salt-sensitive wild-type (SSWT) and SSLepRmutant rats. However, by 18 wk of age, the SSLepRmutant strain developed hypertension, while the elevation in mean arterial pressure was not as severe in SSWTrats (192 ± 4 and 149 ± 6 mmHg, respectively). At baseline, proteinuria was fourfold higher in SSLepRmutant than SSWTrats and remained elevated throughout the study. The early development of progressive proteinuria was associated with renal hyperfiltration followed by a decline in renal function over the course of study in the SSLepRmutant compared with SSWTrats. Kidneys from the SSLepRmutant strain displayed more glomerulosclerosis and glomerular lipid accumulation than SSWTrats. Glomeruli were isolated from the renal cortex of both strains at 6 and 18 wk of age, and RNA sequencing was performed to identify genes and pathways driving glomerular injury. We observed significant increases in expression of the influx lipid transporters, chemokine (C-X-C motif) ligand 16 (Cxcl16) and scavenger receptor and fatty acid translocase (Cd36), respectively, and a significant decrease in expression of the efflux lipid transporter, ATP-binding cassette subfamily A member 2 ( Abca2; cholesterol efflux regulatory protein 2), in SSLepRmutant compared with SSWTrats at 6 and 18 wk of age, which were validated by RT-PCR analysis. These data suggest an association between glomerular hyperfiltration and glomerular lipid accumulation during the early development of proteinuria associated with obesity. |
| Databáze: | OpenAIRE |
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