In:
Clinical and Experimental Pharmacology and Physiology, Wiley, Vol. 47, No. 12 ( 2020-12), p. 1978-1984
Abstract:
Obesity‐related kidney disease is associated with generalized endothelial dysfunction. Liraglutide, a glucagon‐like peptide‐1 agonist, has cardiovascular–renal protective effects in patients with diabetes. In this study, the ability of liraglutide to reduce urinary albumin excretion by alleviating glomerular vascular endothelial growth factor‐nitric oxide (VEGF–NO) axis uncoupling was assessed in high fat diet‐induced obese mice. C57BL/6J mice were divided into control and obesity groups, treated with or without liraglutide (200 μg/kg/day). Blood biochemistry and urinary albumin excretion were measured. Glomerular VEGF and the AMPK–endothelial nitric oxide synthase (eNOS) pathway were assayed by western blotting. Glomerular NO, renal haeme oxygenase‐1 activity, and malondialdehyde levels were also measured. Treatment of obese mice with liraglutide led to significant reductions in body weight gain (46 ± 1 g vs 55 ± 1 g, P 〈 .0001), visceral fat (8.9 ± 0.6 g vs 14.5 ± 0.6 g, P 〈 .0001), perirenal fat (2.9 ± 0.2 g vs 5.4 ± 0.3 g, P 〈 .0001), and free fatty acid (1.71 ± 0.12 mmol/L vs 1.02 ± 0.08 mmol/L, P 〈 .0001). Liraglutide significantly improved glucose homeostasis, which was impaired in obese mice. Liraglutide reduced urinary albumin excretion and glomerular hypertrophy in obese mice. Additionally, liraglutide significantly decreased VEGF and increased glomerular NO production in glomeruli, indicating restoration of the glomerular VEGF–NO axis. Furthermore, liraglutide activated the glomerular AMPK–eNOS pathway in obese mice, upregulated renal haeme oxygenase‐1 activity, and reduced the renal malondialdehyde levels in obese mice. In conclusion, liraglutide reduced microalbuminuria and ameliorated renal injury by alleviating the uncoupling of the glomerular VEGF–NO axis.
Type of Medium:
Online Resource
ISSN:
0305-1870
,
1440-1681
DOI:
10.1111/1440-1681.13391
Language:
English
Publisher:
Wiley
Publication Date:
2020
detail.hit.zdb_id:
2020033-X
SSG:
15,3
