PMID- 26583035
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20151120
LR  - 20200930
IS  - 1743-7075 (Print)
IS  - 1743-7075 (Electronic)
IS  - 1743-7075 (Linking)
VI  - 12
DP  - 2015
TI  - FXR expression is associated with dysregulated glucose and lipid levels in the 
      offspring kidney induced by maternal obesity.
PG  - 40
LID - 10.1186/s12986-015-0032-3 [doi]
LID - 40
AB  - BACKGROUND: Maternal obesity is associated with dysregulation of glucose and 
      lipid metabolism with consequent exposure of the fetus to an abnormal metabolic 
      milieu. It is recognized that maternal obesity predisposes offspring to chronic 
      kidney disease (CKD). We aimed to determine whether the nuclear Farnesoid X 
      receptor (FXR), known to play a role in maintaining homeostasis of glucose and 
      lipid metabolism, is involved in renal injury in offspring of obese mothers. 
      METHODS: Maternal obesity was established in a rat model by feeding dams with 
      high-fat diet prior to and during pregnancy and lactation. The offspring's 
      kidneys were examined at postnatal Day 1and Day 20. Human kidney 2 (HK2) cells 
      were exposed to high glucose with or without the FXR agonist GW4064 or when FXR 
      mRNA was silenced. RESULTS: Glucose intolerance in the offspring of obese mothers 
      was evident at weaning, with associated downregulation of renal FXR expression 
      and upregulation of monocyte chemoattractant protein-1 (MCP-1) and transforming 
      growth factor-beta1 (TGF-beta1). HK2 cells exposed to high glucose had reduced FXR 
      expression and increased MCP-1, TGF-beta1, fibronectin and collagen IV expression, 
      which was reversed in the presence of GW4064. FXR-silenced HK2 cells had 
      amplified pro-inflammatory and pro-fibrotic markers under high glucose 
      conditions. CONCLUSIONS: Maternal obesity influences renal expression of 
      pro-inflammatory and fibrotic factors that predispose the offspring to CKD. This 
      was associated with the downregulation of the renal FXR expression suggesting a 
      potential protective role for FXR.
FAU - Glastras, Sarah J
AU  - Glastras SJ
AD  - Kolling Institute, Department of Medicine, University of Sydney, Sydney, 
      Australia ; Department of Endocrinology, Diabetes and Metabolism, Royal North 
      Shore Hospital, St Leonards, Australia.
FAU - Wong, Muh Geot
AU  - Wong MG
AD  - Kolling Institute, Department of Medicine, University of Sydney, Sydney, 
      Australia.
FAU - Chen, Hui
AU  - Chen H
AD  - School of Life Sciences, Faculty of Science, University of Technology Sydney, 
      Sydney, Australia.
FAU - Zhang, Jie
AU  - Zhang J
AD  - Kolling Institute, Department of Medicine, University of Sydney, Sydney, 
      Australia.
FAU - Zaky, Amgad
AU  - Zaky A
AD  - Kolling Institute, Department of Medicine, University of Sydney, Sydney, 
      Australia.
FAU - Pollock, Carol A
AU  - Pollock CA
AD  - Kolling Institute, Department of Medicine, University of Sydney, Sydney, 
      Australia.
FAU - Saad, Sonia
AU  - Saad S
AD  - Kolling Institute, Department of Medicine, University of Sydney, Sydney, 
      Australia.
LA  - eng
PT  - Journal Article
DEP - 20151114
PL  - England
TA  - Nutr Metab (Lond)
JT  - Nutrition & metabolism
JID - 101231644
PMC - PMC4650952
OTO - NOTNLM
OT  - Chronic kidney disease
OT  - Developmental programming
OT  - Farnesoid X receptor
OT  - Maternal obesity
OT  - Nuclear hormone receptor
OT  - Renal injury
EDAT- 2015/11/20 06:00
MHDA- 2015/11/20 06:01
PMCR- 2015/11/14
CRDT- 2015/11/20 06:00
PHST- 2015/05/19 00:00 [received]
PHST- 2015/10/14 00:00 [accepted]
PHST- 2015/11/20 06:00 [entrez]
PHST- 2015/11/20 06:00 [pubmed]
PHST- 2015/11/20 06:01 [medline]
PHST- 2015/11/14 00:00 [pmc-release]
AID - 32 [pii]
AID - 10.1186/s12986-015-0032-3 [doi]
PST - epublish
SO  - Nutr Metab (Lond). 2015 Nov 14;12:40. doi: 10.1186/s12986-015-0032-3. eCollection 
      2015.