Nutritional programming in the rat is linked to long-lasting changes in nutrient sensing and energy homeostasis in the hypothalamus.
BACKGROUND
Nutrient deficiency during perinatal development is associated with an increased risk to develop obesity, diabetes and hypertension in the adulthood. However, the molecular mechanisms underlying the developmental programming of the metabolic syndrome remain largely unknown.


RESULTS
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 days-old rats born to dams fed either a control (200 g/kg) or a low-protein (80 g/kg) diet through 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. Further bioinformatic analysis of the data revealed that perinatal protein restriction permanently alters the expression of two gene clusters regulating common cellular processes. The first one includes several gate keeper genes regulating insulin signaling and 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.


CONCLUSIONS
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 resource for further investigating the role of the hypothalamus in the programming of the metabolic syndrome.
INRA, UMR1280 Physiologie des Adaptations Nutritionnelles, Université de Nantes, Nantes Atlantique Université, Nantes, France.
Ricardo
R
Orozco-Solís
Rhowena J B
RJ
Matos
Omar
O
Guzmán-Quevedo
Sandra
S
Lopes de Souza
Audrey
A
Bihouée
Rémi
R
Houlgatte
Raul
R
Manhães de Castro
Francisco
F
Bolaños-Jiménez
D000818:Animals; D004032:Diet; D004734:Energy Metabolism; D005260:Female; D020869:Gene Expression Profiling; D006706:Homeostasis; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014158:Transcription, Genetic