Abstract
BackgroundMaternal 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.MethodsMaternal 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.ResultsGlucose 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-β1 (TGF-β1). HK2 cells exposed to high glucose had reduced FXR expression and increased MCP-1, TGF-β1, 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.ConclusionsMaternal 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12986-015-0032-3) contains supplementary material, which is available to authorized users.
Highlights
Obesity is increasing in pandemic proportions worldwide, both in Western countries such as the United States and Australia and in developing countries [1, 2]
We aimed to investigate the effect of maternal obesity on the risk of chronic kidney disease (CKD) in the offspring in a rodent model and determine whether dysregulation of Farnesoid X receptor (FXR) expression is involved in this process
Effect of maternal obesity on the offspring of obese mothers Offspring of obese mothers had no difference in body weight at postnatal Day 1, compared to offspring of lean mothers (6.65 ± 0.42 vs. 6.68 ± 0.57 g)
Summary
Obesity is increasing in pandemic proportions worldwide, both in Western countries such as the United States and Australia and in developing countries [1, 2]. Obesity clearly presents a personal risk for a range of future chronic disease, but when occurs during pregnancy and lactation has been shown to increase the risk of future chronic disease in the offspring [3,4,5]. Offspring born to obese mothers are at increased risk of cardiovascular disease, stroke, diabetes and obesity itself [3, 5, 11]. Animal models are a useful means by which to examine the effect of maternal obesity during pregnancy and lactation on offspring without the confounding factors of genetic background and adult lifestyle. 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
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
