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Maternal nutrient restriction during early fetal kidney development attenuates the renal innate inflammatory response in obese young adult offspring
- Source :
- The American Journal of Physiology. Nov, 2009, Vol. 297 Issue 5, pF1199, 9 p.
- Publication Year :
- 2009
-
Abstract
- Obesity is an independent risk factor for developing chronic kidney disease. Toll-like receptor 4 (TLR4), interleukin (IL)-18, and uncoupling protein 2 (UCP2) are important components of the innate immune system mediating inflammatory renal damage. Early to midgestation maternal nutrient restriction appears to protect the kidney from the deleterious effects of early onset obesity, although the mechanisms remain unclear. We examined the combined effects of gestational maternal nutrient restriction during early fetal kidney development and early onset obesity on the renal innate immune response in offspring. Pregnant sheep were randomly assigned to a normal (control, 100%) or nutrient-restricted (NR, 50%) diet from days 30 to 80 gestation and 100% thereafter. Offspring were killed humanely at 7 days or, following rearing in an obesogenic environment, at 1 yr of age, and renal tissues were collected. IL-18 and TLR4 expression were strongly correlated irrespective of intervention. Seven-day NR offspring had significantly lower relative renal mass and IL-18 mRNA expression. At 1 yr of age, obesity resulted in increased mRNA abundance of TLR4, IL-18, and UCP2, coupled with tubular atrophy and greater immunohistological staining of glomerular IL-6 and medullary tumor necrosis factor (TNF)-[alpha]. NR obese offspring had a marked reduction of TLR4 abundance and renal IL-6 staining. In conclusion, maternal nutrient restriction during early fetal kidney development attenuates the effects of early onset obesity-related nephropathy, in part, through the downregulation of the innate inflammatory response. A better understanding of maternal nutrition and the in utero nutritional environment may offer therapeutic strategies aimed at reducing the burden of later kidney disease. interleukin-18; interleukin-6; Toll-like receptor 4; uncoupling protein 2; nephropathy; nutrition doi: 10.1152/ajprenal.00303.2009.
- Subjects :
- Kidney diseases -- Risk factors
Kidney diseases -- Development and progression
Kidney diseases -- Prevention
Kidney diseases -- Research
Natural immunity -- Physiological aspects
Natural immunity -- Research
Obesity -- Complications and side effects
Obesity -- Research
Pregnant women -- Physiological aspects
Pregnant women -- Food and nutrition
Biological sciences
Subjects
Details
- Language :
- English
- ISSN :
- 00029513
- Volume :
- 297
- Issue :
- 5
- Database :
- Gale General OneFile
- Journal :
- The American Journal of Physiology
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.212410573