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RESEARCH ARTICLE

Suboptimal maternal nutrition during early fetal kidney development specifically promotes renal lipid accumulation following juvenile obesity in the offspring

H. P. Fainberg A B , D. Sharkey A , S. Sebert A , V. Wilson A , M. Pope A , H. Budge A and M. E. Symonds A C
+ Author Affiliations
- Author Affiliations

A Early Life Nutrition Research Unit, Academic Child Health, School of Medicine, University Hospital, Nottingham NG7 2UH, UK.

B Present address: School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Leicestershire LE12 5RD, UK.

C Corresponding author. Email: michael.symonds@nottingham.ac.uk

Reproduction, Fertility and Development 25(5) 728-736 https://doi.org/10.1071/RD12037
Submitted: 14 February 2012  Accepted: 6 June 2012   Published: 30 July 2012

Abstract

Reduced maternal food intake between early-to-mid gestation results in tissue-specific adaptations in the offspring following juvenile-onset obesity that are indicative of insulin resistance. The aim of the present study was to establish the extent to which renal ectopic lipid accumulation, as opposed to other markers of renal stress, such as iron deposition and apoptosis, is enhanced in obese offspring born to mothers nutrient restricted (NR) throughout early fetal kidney development. Pregnant sheep were fed either 100% (control) or NR (i.e. fed 50% of their total metabolisable energy requirement from 30–80 days gestation and 100% at all other times). At weaning, offspring were made obese and, at approximately 1 year, kidneys were sampled. Triglyceride content, HIF-1α gene expression and the protein abundance of the outer-membrane transporter voltage-dependent anion-selective channel protein (VDAC)-I on the kidney cortex were increased in obese offspring born to NR mothers compared with those born to controls, which exhibited increased iron accumulation within the tubular epithelial cells and increased gene expression of the death receptor Fas. In conclusion, suboptimal maternal nutrition coincident with early fetal kidney development results in enhanced renal lipid deposition following juvenile obesity and could accelerate the onset of the adverse metabolic, rather than cardiovascular, symptoms accompanying the metabolic syndrome.

Additional keywords: pregnancy, sheep.


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