Hypertension and impaired renal function accompany juvenile obesity: the effect of prenatal diet.
Obesity has been suggested to have a detrimental impact on kidney structure and function, leading to focal glomerulosclerosis and hypertension. It is also associated with hyperleptinemia and elevated renal sympathetic nerve activity. Prenatal undernutrition promotes postnatal obesity, hypertension, and an altered renal structure and function. In this study, we examined the effects of prenatal nutrient restriction and juvenile obesity in sheep. We found that juvenile obesity led to chronic hyperleptinemia and reduced renal function as assessed by nuclear scintigraphy. Additional factors include hypertension, glomerulosclerosis, and increased kidney apoptosis. Prenatal undernutrition, synchronous with early kidney development, coupled postnatally with juvenile obesity had no effect on systemic pathophysiological sequalae associated with obesity per se. Hypertension, hyperleptinemia, and poor renal function were all observed in this group. All indices of renal pathology such as increased expression of proinflammatory cytokines, angiotensin II, glucocorticoid receptors, and increased apoptosis and glomerulosclerosis were entirely absent in obese prenatally undernourished offspring. Our data indicate that juvenile obesity per se leads to systemic hypertension and renal structural and functional pathology. Prenatal undernutrition effectively abolishes any renal histopathology associated with juvenile obesity.
Williams
P J
PJ
School of Human Development, Centre for Reproduction and Early Life, University Hospital, Nottingham, UK.
Kurlak
L O
LO
Perkins
A C
AC
Budge
H
H
Stephenson
T
T
Keisler
D
D
Symonds
M E
ME
Gardner
D S
DS
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D017209:Apoptosis / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D004032:Diet; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006339:Heart Rate / Q000502:physiology; D006973:Hypertension / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D007674:Kidney Diseases / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control; D020738:Leptin / Q000097:blood / Q000502:physiology; D044342:Malnutrition / Q000150:complications*; D009765:Obesity / Q000150:complications* / Q000503:physiopathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011897:Random Allocation; D012756:Sheep
D020738:Leptin