Modeling the impact of growth and leptin deficits on the neuronal regulation of blood pressure

Baiba Steinbrekera; Robert Roghair

doi:10.1530/JOE-16-0273

Back

Modeling the impact of growth and leptin deficits on the neuronal regulation of blood pressure

Journal article

Open access

Peer reviewed

Modeling the impact of growth and leptin deficits on the neuronal regulation of blood pressure

Baiba Steinbrekera and Robert Roghair

Journal of endocrinology, Vol.231(2), pp.R47-R60

11/2016

DOI: 10.1530/JOE-16-0273

PMCID: PMC5148679

PMID: 27613336

Files and links (1)

url

https://doi.org/10.1530/JOE-16-0273View

Published (Version of record) Open Access

Abstract

The risk of hypertension is increased by intrauterine growth restriction (IUGR) and preterm birth. In the search for modifiable etiologies for this life-threatening cardiovascular morbidity, a number of pathways have been investigated, including excessive glucocorticoid exposure, nutritional deficiency and aberration in sex hormone levels. As a neurotrophic hormone that is intimately involved in the cardiovascular regulation and whose levels are influenced by glucocorticoids, nutritional status and sex hormones, leptin has emerged as a putative etiologic and thus a therapeutic agent. As a product of maternal and late fetal adipocytes and the placenta, circulating leptin typically surges late in gestation and declines after delivery until the infant consumes sufficient leptin-containing breast milk or accrues sufficient leptin-secreting adipose tissue to reestablish the circulating levels. The leptin deficiency seen in IUGR infants is a multifactorial manifestation of placental insufficiency, exaggerated glucocorticoid exposure and fetal adipose deficit. The preterm infant suffers from the same cascade of events, including separation from the placenta, antenatal steroid exposure and persistently underdeveloped adipose depots. Preterm infants remain leptin deficient beyond term gestation, rendering them susceptible to neurodevelopmental impairment and subsequent cardiovascular dysregulation. This pathologic pathway is efficiently modeled by placing neonatal mice into atypically large litters, thereby recapitulating the perinatal growth restriction-adult hypertension phenotype. In this model, neonatal leptin supplementation restores the physiologic leptin surge, attenuates the leptin-triggered sympathetic activation in adulthood and prevents leptin- or stress-evoked hypertension. Further pathway interrogation and clinical translation are needed to fully test the therapeutic potential of perinatal leptin supplementation.

Adiposity

Adult

Animals

Animals, Newborn

Disease Models, Animal

Female

Fetal Growth Retardation - drug therapy

Fetal Growth Retardation - metabolism

Fetal Growth Retardation - physiopathology

Hormone Replacement Therapy

Humans

Hypertension - etiology

Hypertension - metabolism

Hypertension - prevention & control

Hypothalamus - metabolism

Infant, Newborn

Infant, Premature

Infant, Premature, Diseases - drug therapy

Infant, Premature, Diseases - metabolism

Infant, Premature, Diseases - physiopathology

Leptin - deficiency

Leptin - genetics

Leptin - metabolism

Leptin - therapeutic use

Male

Mice

Nerve Tissue Proteins - agonists

Nerve Tissue Proteins - metabolism

Neurodevelopmental Disorders - drug therapy

Neurodevelopmental Disorders - metabolism

Neurodevelopmental Disorders - physiopathology

Pregnancy

Receptors, Leptin - agonists

Receptors, Leptin - metabolism

Recombinant Proteins - metabolism

Recombinant Proteins - therapeutic use

Signal Transduction

Details

Title: Subtitle: Modeling the impact of growth and leptin deficits on the neuronal regulation of blood pressure
Creators: Baiba Steinbrekera - University of Iowa
Robert Roghair - University of Iowa
Resource Type: Journal article
Publication Details: Journal of endocrinology, Vol.231(2), pp.R47-R60
DOI: 10.1530/JOE-16-0273
PMID: 27613336
PMCID: PMC5148679
ISSN: 0022-0795
eISSN: 1479-6805
Grant note: T35 HL007485 / NHLBI NIH HHS R01 HL102659 / NHLBI NIH HHS
Language: English
Date published: 11/2016
Academic Unit: Stead Family Department of Pediatrics; Neonatology
Record Identifier: 9984354147802771

Metrics

12 Record Views

19 Times Cited - Web of Science

See more details