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2017 ; 15
(7
): 344-353
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Mast Cell and M1 Macrophage Infiltration and Local Pro-Inflammatory Factors Were
Attenuated with Incretin-Based Therapies in Obesity-Related Glomerulopathy
#MMPMID28737448
He J
; Yuan G
; Cheng F
; Zhang J
; Guo X
Metab Syndr Relat Disord
2017[Sep]; 15
(7
): 344-353
PMID28737448
show ga
BACKGROUND: The global increase of obesity parallels the obesity-related
glomerulopathy (ORG) epidemic. Dipeptidyl peptidase 4 inhibitors and
glucagon-like peptide-1 receptor agonists were well recognized to attenuate renal
injury independent of glucose control in diabetic nephropathy. There are limited
studies focusing on their effects on ORG. We explored the effects of
incretin-based therapies on early ORG and the inflammatory responses involved
mainly concentrated on mast cell (MC) and macrophage (M) infiltration and local
pro-inflammatory factors. METHODS: ORG rat models were induced by high-fat diet
and then divided into ORG vehicle, vildagliptin (3?mg/kg/day, qd) and liraglutide
(200??g/kg, bid) treated groups. After 8 weeks of treatments, albuminuria,
glomerular histology, renal inflammatory cell infiltration, and pro-inflammatory
factors were analyzed. RESULTS: Early ORG model was demonstrated by albuminuria,
glomerulomegaly, foot process fusion, and mesangial and endothelial mild
proliferation. Incretin-based therapies limited body weight gain and improved
insulin sensitivity. ORG was alleviated, manifested by decreased average
glomerular area, attenuated mesangial and endothelial cell proliferation, and
revived cell-to-cell propagation of podocytes, which contributed to reduced
albuminuria. Compared with ORG vehicle, MC and M1 macrophage (pro-inflammatory)
infiltration and M1/M2 ratio were significantly decreased; M2 macrophage
(anti-inflammatory) was not significantly increased after incretin-based
treatments. Tumor necrosis factor-? (TNF-?) and IL-6 in renal cortex were
significantly downregulated, while transforming growth factor-?1 (TGF-?1)
remained unchanged. CONCLUSIONS: Incretin-based treatments could alleviate
high-fat diet-induced ORG partly through the systemic insulin sensitivity
improvement and the attenuated local inflammation, mainly by the decrease of MC
and M1 macrophage infiltration and reduction of TNF-? and IL-6.