title: Exposure to a high-fat diet during development alters leptin and ghrelin sensitivity and elevates renal sympathetic nerve activity and arterial pressure in rabbits.
abstract: Exposure to maternal obesity or a maternal diet rich in fat during development may have adverse outcomes in offspring, such as the development of obesity and hypertension. The present study examined the effect of a maternal high-fat diet (m-HFD) on offspring blood pressure and renal sympathetic nerve activity, responses to stress, and sensitivity to central administration of leptin and ghrelin. Offspring of New Zealand white rabbits fed a 13% HFD were slightly heavier than offspring from mothers fed a 4% maternal normal fat diet (P<0.05) but had 64% greater fat pad mass (P=0.015). Mean arterial pressure, heart rate, and renal sympathetic nerve activity at 4 months of age were 7%, 7%, and 24% greater, respectively (P<0.001), in m-HFD compared with maternal normal fat diet rabbits, and the renal sympathetic nerve activity response to airjet stress was enhanced in the m-HFD group. m-HFD offspring had markedly elevated pressor and renal sympathetic nerve activity responses to intracerebroventricular leptin (5-100 µg) and enhanced sympathetic responses to intracerebroventricular ghrelin (1-5 nmol). In contrast, there was resistance to the anorexic effects of intracerebroventricular leptin and less neuronal activation as detected by Fos immunohistochemistry in the arcuate (-57%; P<0.001) and paraventricular (-37%; P<0.05) nuclei of the hypothalamus in m-HFD offspring compared with maternal normal fat diet rabbits. We conclude that offspring from mothers consuming an HFD exhibit an adverse cardiovascular profile in adulthood because of altered central hypothalamic sensitivity to leptin and ghrelin.
authors.affiliation: Baker IDI Heart and Diabetes Institute, 75 Commercial Rd, Melbourne, Victoria 3004, Australia. Geoff.head@bakeridi.edu.au.
authors.forename: Larissa J
authors.initials: LJ
authors.lastname: Prior
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Davern
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Burke
authors.forename: Kyungjoon
authors.initials: K
authors.lastname: Lim
authors.forename: James A
authors.initials: JA
authors.lastname: Armitage
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Head
mesh_terms: D050154:Adiposity / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004041:Dietary Fats / Q000494:pharmacology*; D005260:Female; D054439:Ghrelin / Q000378:metabolism* / Q000494:pharmacology; D006977:Hypertension, Renal / Q000378:metabolism / Q000503:physiopathology*; D007668:Kidney / Q000294:innervation / Q000502:physiology; D020738:Leptin / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D009929:Organ Size / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism / Q000503:physiopathology*; D011817:Rabbits; D013312:Stress, Physiological / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D004041:Dietary Fats; D054439:Ghrelin; D020738:Leptin
keywords: blood pressure; heart rate; leptin; obesity; rabbits; sympathetic nervous system