PMID- 28737448
OWN - NLM
STAT- MEDLINE
DCOM- 20180607
LR  - 20181202
IS  - 1557-8518 (Electronic)
IS  - 1540-4196 (Print)
IS  - 1540-4196 (Linking)
VI  - 15
IP  - 7
DP  - 2017 Sep
TI  - Mast Cell and M1 Macrophage Infiltration and Local Pro-Inflammatory Factors Were 
      Attenuated with Incretin-Based Therapies in Obesity-Related Glomerulopathy.
PG  - 344-353
LID - 10.1089/met.2017.0057 [doi]
AB  - 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 mug/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-alpha (TNF-alpha) and IL-6 in renal cortex were 
      significantly downregulated, while transforming growth factor-beta1 (TGF-beta1) 
      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-alpha and IL-6.
FAU - He, Jiao
AU  - He J
AD  - Department of Endocrinology, Peking University First Hospital , Beijing, People's 
      Republic of China .
FAU - Yuan, Geheng
AU  - Yuan G
AD  - Department of Endocrinology, Peking University First Hospital , Beijing, People's 
      Republic of China .
FAU - Cheng, Fangxiao
AU  - Cheng F
AD  - Department of Endocrinology, Peking University First Hospital , Beijing, People's 
      Republic of China .
FAU - Zhang, Junqing
AU  - Zhang J
AD  - Department of Endocrinology, Peking University First Hospital , Beijing, People's 
      Republic of China .
FAU - Guo, Xiaohui
AU  - Guo X
AD  - Department of Endocrinology, Peking University First Hospital , Beijing, People's 
      Republic of China .
LA  - eng
PT  - Journal Article
DEP - 20170724
PL  - United States
TA  - Metab Syndr Relat Disord
JT  - Metabolic syndrome and related disorders
JID - 101150318
RN  - 0 (Dipeptidyl-Peptidase IV Inhibitors)
RN  - 0 (Incretins)
RN  - 0 (Interleukin-6)
RN  - 0 (Nitriles)
RN  - 0 (Pyrrolidines)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 839I73S42A (Liraglutide)
RN  - AYI8EX34EU (Creatinine)
RN  - EC 3.4.14.5 (DPP4 protein, rat)
RN  - EC 3.4.14.5 (Dipeptidyl Peptidase 4)
RN  - I6B4B2U96P (Vildagliptin)
RN  - PJY633525U (Adamantane)
SB  - IM
MH  - Adamantane/analogs & derivatives/pharmacology
MH  - Albuminuria/metabolism
MH  - Animals
MH  - Creatinine/blood
MH  - Dipeptidyl Peptidase 4/metabolism
MH  - Dipeptidyl-Peptidase IV Inhibitors/pharmacology
MH  - Glucose Tolerance Test
MH  - Incretins/*metabolism
MH  - Inflammation/*metabolism
MH  - Interleukin-6/metabolism
MH  - Kidney Diseases/complications/*metabolism
MH  - Kidney Glomerulus/*pathology
MH  - Liraglutide/pharmacology
MH  - Macrophages/*metabolism
MH  - Male
MH  - Mast Cells/*metabolism
MH  - Nitriles/pharmacology
MH  - Obesity/complications/*metabolism
MH  - Pyrrolidines/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Vildagliptin
PMC - PMC5576269
OTO - NOTNLM
OT  - DPP4
OT  - incretin
OT  - macrophage
OT  - mast cell
OT  - obesity-related glomerulopathy
COIS- No competing financial interests exist.
EDAT- 2017/07/25 06:00
MHDA- 2018/06/08 06:00
PMCR- 2017/09/01
CRDT- 2017/07/25 06:00
PHST- 2017/07/25 06:00 [pubmed]
PHST- 2018/06/08 06:00 [medline]
PHST- 2017/07/25 06:00 [entrez]
PHST- 2017/09/01 00:00 [pmc-release]
AID - 10.1089/met.2017.0057 [pii]
AID - 10.1089/met.2017.0057 [doi]
PST - ppublish
SO  - Metab Syndr Relat Disord. 2017 Sep;15(7):344-353. doi: 10.1089/met.2017.0057. 
      Epub 2017 Jul 24.