Protective effects of liraglutide on glomerular podocytes in obese mice by inhibiting the inflammatory factor TNF-alpha-mediated NF-kappa B and MAPK pathway

Objective: To evaluate the protective effects of Glucagon-like peptide-1(GLP-1) receptor agonist (liraglutide) on glomerular podocytes of obese mice, and explore the possible underlying mechanism. Methods: Twelve of the thirty-four healthy and clean male mice were randomly selected as the normal control group. The remaining twenty-two mice were included in the high-fat diet (HFD) feeding group. After twelve weeks of high-fat diet and normal diet, two mice each from the HFD feeding group and the normal control group were randomly selected and sacrificed to suggested that the modeling was successful in the HFD feeding group. Then, twenty mice were randomly divided into HFD + liraglutide group (liraglutide group, n = 10) and HFD group (n = 10). The morphology and the structure of glomerular podocytes were observed using electron microscopy. Podocyte foot process diameter, glomerular basement membrane thickness were measured. ELISA was performed to determine the serum tumor necrosis factor alpha (TNF-alpha) level. The expression levels of TNF-alpha protein and nuclear factor-kappa B (NF-kappa B) in kidney tissues, extracellularsignal regulating kinase(ERK), c-Jun N-terminal kinase (JNK) and p38MAPK in the mitogenactivated protein kinases(MAPK) pathway were detected by western blotting. Results: HFD-feeding caused significant renal injury, podocyte pathological changes, podocyte foot process diameter and glomerular basement membrane thickness were significantly increased compared with the control group. Liraglutide injection significantly alleviated HFD-induced effects on renal functions and podocyte morphology, as 24 h urine protein, urinary albumin and podocyte histomorphology. Moreover, HFD-induced Inflammatory reaction were obviously attenuated by Liraglutide administration, so did the HFD-induced activation of TNF-alpha-mediated NF-kappa B and MAPK pathways. Conclusion: Liraglutide reduced urinary albumin excretion in obesity-related glomerulopathy model mice, and improved podocyte morphology and structural damage. The mechanism may be partly related to the inhibition of TNF-alpha-mediated NF-kappa B and MAPK pathways. (C) 2019 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.