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

Abstract

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.

Effects of Coronary Ischemia-Reperfusion in a Rat Model of Early Overnutrition. Role of Angiotensin Receptors

“…Likewise in obese adolescents, systolic ventricular function may be preserved but diastolic function may present evidence of impairment, which is associated by exercise intolerance [40]. These alterations could be explained, at least in part, by the effect of nutritional conditions on the development of the organs, as it has been reported that perinatal ambient has an important effect on the development of heart or kidney modifying the processes of apoptosis and cell survival [41].…”

Biological Mechanisms for Nutritional Regulation of Maternal Health and Fetal Development

“…Additionally, substantial evidence links IUGR with the aetiology of many chronic diseases in adult humans 15 . These findings have prompted extensive animal studies to identify the biological mechanisms for nutritional regulation of fetal growth and development as well as long‐term health consequences of IUGR, preterm birth, and other poor pregnancy outcomes 16–21 . This paper highlights the recent advances in this area of biomedical research, with a focus on effects of macronutrients and micronutrients on adverse pregnancy outcomes, including maternal morbidity and mortality, infant morbidity and mortality, as well as fetal and infant growth and development.…”