Hypertension and impaired renal function accompany juvenile obesity: The effect of prenatal diet

Williams, Phyllis H.; Kurlak, Lesia O.; Ac, Perkins; Budge, Helen; Stephenson, Terence; Keisler, D.H.; Symonds, Michael; Gardner, David

doi:10.1038/sj.ki.5002276

Cited by 49 publications

(84 citation statements)

References 57 publications

(72 reference statements)

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“…Similar findings have been reported by other groups (13). In addition, we have shown that adolescent-onset obesity results in marked renal inflammation, apoptosis, and glomerulosclerosis in young adults compared with lean control animals (37). Moreover, when maternal nutrient restriction, from early to midgestation, precedes the onset of obesity in offspring, we see a marked attenuation of these effects in young adults potentially confer-ring an element of renal protection from obesity-related nephropathy (37).…”

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confidence: 75%

Maternal nutrient restriction during early fetal kidney development attenuates the renal innate inflammatory response in obese young adult offspring

Sharkey¹,

Gardner

Symonds

et al. 2009

American Journal of Physiology-Renal Physiology

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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)-α. 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.

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supporting

confidence: 75%

Maternal nutrient restriction during early fetal kidney development attenuates the renal innate inflammatory response in obese young adult offspring

Sharkey¹,

Gardner

Symonds

et al. 2009

American Journal of Physiology-Renal Physiology

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“…This situation results, at least in part, from the complexity of the biological processes involved and the challenge of effecting lifestyle changes in activity and dietary intake. At the same time, the causes of the ongoing epidemic of obesity, and the predicted increase in associated renal diseases and CVD, are multifactorial (4) and may be either exacerbated, or reduced, by early dietary exposure (5) . One consistent theme that is apparent from both historical and contemporary studies is that changes in nutrition at specific stages of pregnancy can have very different outcomes (6) .…”

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confidence: 99%

Nutritional models of the developmental programming of adult health and disease

Symonds

Budge

2009

Proc. Nutr. Soc.

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The ability to not only replicate but also extend the findings from both historical epidemiological studies and contemporary cohorts of the developmental programming of later disease are critical if the mechanisms by which early diet impacts on later disease are to be fully understood. To date, a plethora of models have been established, with the range including global changes in dietary input, imbalanced diets and diets deficient in single nutrients. Key factors in translating these findings to the human situation are the pronounced differences in the relative growth and development between large and small mammals from the time of conception through pregnancy, lactation and weaning. This disparity is reflected in the very different nutritional requirements between species and the substantial divergence between rodents and large animals in the ontogeny of many of the organ systems that are nutritionally regulated. For example, hypothalamic circuitry is much more developed in species with a long gestation and offspring are born with a mature hypothalamic-pituitary axis in sheep and man compared with mice and rats. Similarly, nephron number is established towards the end of gestation in large mammals compared with the lactational period in rats. These types of differences will impact on the ability of individual and combined nutritional interventions to reset developmental processes, and may be further compounded by the gender of a fetus. The challenge for future work in this exciting and dynamic area of research is to utilise these marked comparative differences to generate imaginative nutritional interventions in order to improve the viability, health and well-being of the offspring.

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“…In the heart and in the kidney, significant changes occurred in gene expression between the maternal nutrient-restricted group and their obese controls, principally of factors associated with exposure to cytokines and angiotensin II, possibly suggesting an enhanced adaptation to obesity (40) . However, similar increases in haemodynamic parameters may suggest similar vasomotor afferent responses in both obese groups to the RAS, which also include extensive cell proliferation, particularly of mesangial and proximal tubular endothelial cells (36) .…”

Section: The Combined Effects Of Maternal Nutrient Restriction and Obmentioning

confidence: 99%

“…Between the different animal models studied, the ovine model, due its relatively long pregnancy (145 d) and its ability to produce an offspring of similar weight to human subjects, with fully developed organs, has proven to be useful for increasing the understanding of the effects of changes in maternal diet at specific stages of pregnancy (38) . In different ovine studies, it was observed that a reduction of 50% in maternal food intake up to mid-gestation (days 30 to 80 (145 d to full-term)) produced an offspring of weight similar to those born to control-fed mothers (39,40) . However, as noted in the human Dutch winter cohorts, kidney physiology, blood pressure and fat mass were affected at different points in the offspring's life (39,41,42) .…”

Section: Changes In Maternal Diet During Mid-gestation In Sheep and Tmentioning

confidence: 99%

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The conflicting effects of maternal nutrient restriction and early-life obesity on renal health

Fainberg

Budge²,

Symonds³

2011

Proc. Nutr. Soc.

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Epidemiological and animal studies have demonstrated that early-life nutrition alters the metabolic responses and generates structural changes in complex tissues, such as the kidneys, which may lead to a reduction in the offspring lifespan. Independently, obesity induces a spontaneous low-grade chronic inflammatory response by modulating several of the major metabolic pathways that ultimately compromise long-term renal health. However, the combined effects of maternal nutrition and early-life obesity in the development of renal diseases are far from conclusive. Previous results, using the ovine model, demonstrated that the combination of a reduction in fetal nutrition and juvenile obesity induced a series of adaptations associated with severe metabolic syndrome in the heart and adipose tissue. Surprisingly, exposure to an obesogenic environment in the kidney of those offspring produced an apparent reduction in glomerulosclerosis in relation to age-and weight-matched controls. However, this reduction in cellular apoptosis was accompanied by a rise in glomerular filtration rate and blood pressure of equal intensity when compared with obese controls. The intention of this review is to explain the adaptive responses observed in this model, based on insights into the mechanism of renal fetal programming, and their potential interactions with some of the metabolic changes produced by obesity. Maternal nutrient restriction: Renal health: Fetal programmingDeterioration in renal health is the result of both heritable and environmental factors which, in turn, influence the rate of functional decline. A clear environmental factor that reduces kidney function is that produced with chronic inflammation and induced by metabolic disorders, such as obesity (1,2) . A good example of the intricate relationship between the nutritional environment and metabolic-renalassociated diseases at the population level is observed in previously underdeveloped countries, such as China, a society that has experienced rapid growth in the prevalence of obesity due to several changes in lifestyle (3) . In less than a generation, medical conditions associated with overweight or obesity, including type 2 diabetes, hypertension and renal diseases, have increased to unprecedented levels, matching those existing in western developed countries. Unfortunately, this rapid change in the nutritional environment has exposed an inherent human vulnerability to the complications of excess weight gain particularly in young children (3) . In an attempt to explain the effects of early-life nutrition observed in previous epidemiological studies and their association with the development of metabolic complications in later life, Barker and Hales proposed the 'thrifty phenotype hypothesis' (4) . The basis of this hypothesis is that the maternal nutritional environment and early postnatal life nutrition play a major role in the pathogenesis of Abbreviations: GH, growth hormone; IGF, insulin-like growth factor; RAS, renin-angiotensin system.

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Hypertension and impaired renal function accompany juvenile obesity: The effect of prenatal diet

Cited by 49 publications

References 57 publications

Maternal nutrient restriction during early fetal kidney development attenuates the renal innate inflammatory response in obese young adult offspring

Maternal nutrient restriction during early fetal kidney development attenuates the renal innate inflammatory response in obese young adult offspring

Nutritional models of the developmental programming of adult health and disease

The conflicting effects of maternal nutrient restriction and early-life obesity on renal health

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