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Maternal low protein diet decreases leptin expression in the brains of the neonatal rat offspring
Author(s) -
Marwarha Gurdeep,
Claycombe Kate,
Ghribi Othman
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb474
Subject(s) - offspring , endocrinology , medicine , leptin , biology , gestation , basal (medicine) , transactivation , transcription factor , pregnancy , obesity , gene , biochemistry , genetics , insulin
Maternal low protein (LP) diets during gestation cause learning and memory impairment as well as cognitive deficits in the neonatal and adult offspring. The cellular and molecular mechanism that mediate the deleterious effects of prenatal exposure to a maternal LP diet on cognitive function is egregiously understood. Leptin, an adipocytokine expressed endogenously in the brain, exhibits pleiotropic effects in the brain and plays an indispensable role in learning and memory, as well as neuronal survival. In this study, we show that prenatal exposure to a maternal LP diet results in the mitigation of basal expression of leptin in the brains of the neonatal rat offspring. Sprague‐Dawley female rats were fed either a 20% normal protein diet (NP) or an 8% low protein (LP) diet inducted at three weeks before breeding and continued for the entirety of the gestation period. Prenatal exposure to a maternal LP diet resulted in reduced leptin expression in the brains of the neonatal offspring that was ascribed to a reduction in the C/EBPα and C/EBPβ – mediated transactivation of the leptin promoter. We further delved into and delineated the upstream molecular mediators and elucidated the role of lower CREB‐mediated transcription of C/EBPα and C/EBPβ that resulted in a reduction of the basal expression of C/EBPα and C/EBPβ leading to a significant attenuation in their transcriptional activities in the brains of the neonatal progeny prenatally exposed to a maternal LP diet. This decrease in transcriptional activity of C/EBPα and C/EBPβ results in the attenuation of the basal leptin promoter activity. Furthermore, maternal LP diet also induces a reduction in the enrichment of the acetylated histones in the nucleosomes that envelope the leptin promoter thereby making it refractory to trans‐activation. Our study unveils a mitigation of leptin expression in the brain as a novel mechanistic insight and a conduit into the deleterious effects evoked by prenatal exposure to a maternal LP diet on cognitive function. Support or Funding Information This work was supported by National Institutes of Health, Grant # R01AG0145264, to Dr. Othman Ghribi.