Postnatal early overnutrition causes long-term renal decline in aging male rats

Abstract

Background:We evaluated the influence of postnatal early overnutrition on renal pathophysiological changes in aging rats. Methods: Three or 10 male pups per mother were assigned to either the small litter (SL) or normal litter (control) groups, respectively, during the first 21 d of life. The effects of early postnatal overnutrition were determined at 12 mo. results: SL rats weighed more than controls between 4 d and 6 mo of age (P < 0.05). However, between 6 and 12 mo, body weights in both groups were not different. In the SL group, at 12 mo, systolic blood pressure was higher and creatinine clearance was lower than the same in controls (P < 0.05). Numbers of CD68 (ED1)-positive macrophages and apoptotic cells in renal cortex were higher in SL rats (P < 0.05). Furthermore, index scores for glomerulosclerosis and tubulointerstitial fibrosis were higher in the SL group (P < 0.05). Significantly less glomeruli per section area were found in aging SL rats (P < 0.05). Immunoblotting and immunohistochemistry showed decreased intrarenal renin expression in SL rats (P < 0.05). conclusion: Early postnatal overnutrition can potentiate structural and functional abnormalities in the aging kidney and can lead to systolic hypertension with reduced intrarenal renin activity.

Early life obesity and chronic kidney disease in later life

“…Early postnatal overnutrition in 12-month-old male rats leads to systolic HTN, decreased GFR and increased macrophage infiltration, apoptosis, glomerulosclerosis and tubulointerstitial fibrosis in the renal cortex. Neonatally overfed rats had significantly fewer glomeruli and decreased intrarenal renin expression at adulthood than the controls [36]. These findings suggest that early postnatal overnutrition during the suckling period may induce disturbances in renal and cardiac maturation in association with intrarenal and intracardiac RAS dysregulation in young male rats [34,62].…”

“…Inhibiting the RAS during development also results in a reduced number of nephrons, HTN, albuminuria, glomerulosclerosis, renal interstitial inflammation and creatinine retention in these offspring in adulthood [33]. Moreover, our recent data show that altered intrarenal RAS control during renal maturation (increased renin and AT2 receptor activity at 28 days of age) is associated with life-long renal dysfunction in neonatally overfed rats [34][35][36]. Taken together, these findings suggest abnormal regulation of the perinatal RAS may be responsible for renal impairment in adulthood, which is enhanced with age.…”

“…These findings suggest that early postnatal overnutrition during the suckling period may induce disturbances in renal and cardiac maturation in association with intrarenal and intracardiac RAS dysregulation in young male rats [34,62]. Altered RAS control beginning in the neonatal stage can malprogram long-standing renal physiologic regulation and BP levels [34][35][36]. Increased renal workload due to postnatal overnutrition may also provoke glomerular hyperfiltration at the single-nephron level, which in turn can induce glomerulosclerosis, progressive renal dysfunction and HTN [19].…”

“…It is now evident that nutrition is the cornerstone of this association [12] and that postnatal factors and rapid postnatal growth per se may also contribute to the pathogenesis and increased risk of obesity and CKD in later life, even independently of birth weight and prenatal nutrition [35, 36,52]. The mechanisms of renal and cardiovascular risks due to early life nutritional programming remain largely unknown, whereas fundamental biological processes, such as permanent structural changes, accelerated cellular aging and epigenetic regulation, may form integral underlying mechanisms during early life programming [41] (Fig.…”

“…Visceral white adipose tissue, lipogenic activities and inflammatory status increase and glucose/insulin homeostasis is impaired in neonatally overfed rodents [10]. Of note, this rapid postnatal growth per se causes early and late modifications in renal and cardiovascular functions in rodents [10,[34][35][36]52].…”