Glucagon-like peptide-1 analog prevents obesity-related glomerulopathy by inhibiting excessive autophagy in podocytes

American Journal of Physiology. Renal Physiology
Honglei GuoYong Gu

Abstract

To investigate the role of glucagon-like peptide-1 analog (GLP-1) in high-fat diet-induced obesity-related glomerulopathy (ORG). Male C57BL/6 mice fed a high-fat diet for 12 wk were treated with GLP-1 (200 μg/kg) or 0.9% saline for 4 wk. Fasting blood glucose and insulin and the expression of podocin, nephrin, phosphoinositide 3-kinase (PI3K), glucose transporter type (Glut4), and microtubule-associated protein 1A/1B-light chain 3 (LC3) were assayed. Glomerular morphology and podocyte foot structure were evaluated by periodic acid-Schiff staining and electron microscopy. Podocytes were treated with 150 nM GLP-1 and incubated with 400 μM palmitic acid (PA) for 12 h. The effect on autophagy was assessed by podocyte-specific Glut4 siRNA. Insulin resistance and autophagy were assayed by immunofluorescence and Western blotting. The high-fat diet resulted in weight gain, ectopic glomerular lipid accumulation, increased insulin resistance, and fusion of podophyte foot processes. The decreased translocation of Glut4 to the plasma membrane and excess autophagy seen in mice fed a high-fat diet and in PA-treated cultured podocytes were attenuated by GLP-1. Podocyte-specific Glut4 siRNA promoted autophagy, and rapamycin-enhanced autophagy ...Continue Reading

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Citations

Apr 29, 2020·International Journal of Molecular Sciences·Anton I KorbutVadim V Klimontov
Apr 25, 2018·Nature Reviews. Endocrinology·Yingmei ZhangJun Ren
Feb 29, 2020·International Journal of Molecular Sciences·Guangbi LiPin-Lan Li
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Jun 5, 2020·Kidney & Blood Pressure Research·Shuting YangZhiguang Zhou

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Methods Mentioned

BETA
protein Assay
transmission electron microscopy

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