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Title: Nutritional programming of the metabolic syndrome is associated with long-lasting changes in nutrient sensing and energy homeostasis in the hypothalamus as revealed by genome-wide DNA microarray analysis      
keywords:
Transcriptome or Gene expression
ID:
PRJNA128163
description:
Nutrient deficiency during perinatal development is associated with an increased risk to develop obesity, diabetes and hypertension in adulthood. However, the molecular mechanisms underlying the developmental programming of the metabolic syndrome remain largely unknown. Given the essential role of the hypothalamus in the integration of nutritional, endocrine and neuronal cues, here we have analyzed the profile of the hypothalamus transcriptome in 180-day-old rats born to dams fed either a control (200 g/kg) or a low-protein (80 g/kg) diet throughout pregnancy and lactation. From a total of 26,209 examined genes, 688 were up-regulated and 309 down-regulated (P<0.003) by early protein restriction. Based on the hypothesis that variations in gene expression levels often reflect changes in gene’s activity and that transcriptional networks are at the heart of physiological functions, we identified two gene clusters regulating common cellular processes whose expression is coordinately regulated by perinatal protein restriction. The first one is constituted by several genes of the insulin signaling pathway which, additionally, act as gatekeeper genes for regulation of nutrient sensing. The second cluster encompasses a functional network of nuclear receptors and co-regulators of transcription involved in the detection and use of lipid nutrients as fuel which, in addition, link temporal and nutritional cues to metabolism through their tight interaction with the circadian clock. Collectively, these results indicate that the programming of the hypothalamic circuits regulating energy homeostasis is a key step in the development of obesity associated with malnutrition in early life and provide a valuable starting point for the direct and systematic experimental analysis of the role of the hypothalamus in the physiopathological disturbances associated with the programming of the metabolic syndrome. Overall design: Five rats fed a control diet, and five rats fed a low-protein diet. All rats are male.
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landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA128163
authentication:
none
authorization:
none
ID:
pmid:20975839
dateReleased:
07-02-2010
name:
Rattus norvegicus
ncbiID:
ncbitax:10116
abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject