Perinatal nutrient restriction induces long-lasting alterations in the circadian expression pattern of genes regulating food intake and energy metabolism

• Published in: International Journal of Obesity Vol. 35; no. 7; pp. 990 - 1000
• Main Authors: Orozco-Solís, R, Matos, R.J.B, Souza, S. Lopes de, Grit, I, Kaeffer, B, Castro, R Manhães de, Bolaños-Jiménez, F
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.07.2011
• Subjects: Adaptation, Physiological; adulthood; Agouti-related protein; Analysis; Analysis of Variance; Animals; Behavior; Bioenergetics; Biological and medical sciences; Body Weight; cardiovascular diseases; Circadian Clocks - genetics; Circadian rhythm; Circadian rhythms; CLOCK protein; Cocaine; Diet, Protein-Restricted - adverse effects; Diets; Eating - genetics; Energy; energy expenditure; energy intake; Energy metabolism; Enzymes; fatty-acid synthase; Feeding; Female; Food; Food intake; Gene expression; Gene Expression Regulation - physiology; genes; Genes, Regulator - genetics; Glucokinase; Hyperphagia; Hypothalamus; Ingestion; Insulin; insulin resistance; Laboratory animals; lactation; Life Sciences; Liver; Malnutrition; Medical sciences; messenger RNA; Metabolic diseases; Metabolic disorders; Metabolism; neuropeptide Y; Nutrients; Nutrition; Obesity; Other nutritional diseases (malnutrition, nutritional and vitamin deficiencies...); overeating; Peptides; Physiological aspects; Pregnancy; Prenatal Exposure Delayed Effects - genetics; Prenatal Exposure Delayed Effects - physiopathology; pro-opiomelanocortin; progeny; Proteins; pups; quantitative polymerase chain reaction; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; Transcription factors; Undernutrition; Weaning; Brazil; France; Energy metabolism; metabolic programming; Central nervous system; Alteration; Programming; Biological rhythm; Hypothalamus; circadian clock; Encephalon; Biological clock; Gene; Genetics; Malnutrition; Long lasting; Nutritional status; Human; Nutrition; Nutrition disorder; Perinatal; Metabolic diseases; Circadian rhythm; Gene expression; Newborn; Food intake; Nutrient; perinatal undernutrition; low protein diet; adult disease; early infancy; induced obesity; cerebral cortex; peripheral tissue; feeding schedule; messenger rna; locomotor activity; suprachiasmatic nucleus; hypothalamus; food intake
• ISSN: 0307-0565; 1476-5497; 0307-0565
• DOI: 10.1038/ijo.2010.223

Objective: Several lines of evidence indicate that nutrient restriction during perinatal development sensitizes the offspring to the development of obesity, insulin resistance and cardiovascular disease in adulthood via the programming of hyperphagia and reduced energy expenditure. Given the link between the circadian clock and energy metabolism, and the resetting action of food on the circadian clock, in this study, we have investigated whether perinatal undernutrition affects the circadian expression rhythms of genes regulating food intake in the hypothalamus and energy metabolism in the liver. Design: Pregnant Sprague-Dawley rats were fed ad libitum either a control (20% protein) or a low-protein (8% protein) diet throughout pregnancy and lactation. At weaning, pups received a standard diet and at 17 and 35 days of age, their daily patterns of gene expression were analyzed by real-time quantitative PCR experiments. Results: 17-day-old pups exposed to perinatal undernutrition exhibited significant alterations in the circadian expression profile of the transcripts encoding diverse genes regulating food intake, the metabolic enzymes fatty acid synthase and glucokinase as well as the clock genes BMAL1 and Period1. These effects persisted after weaning, were associated with hyperphagia and mirrored the results of the behavioral analysis of feeding. Thus, perinatally undernourished rats exhibited an increased hypothalamic expression of the orexigenic peptides agouti-related protein and neuropeptide Y. Conversely, the mRNA levels of the anorexigenic peptides pro-opiomelanocortin and cocaine and amphetamine-related transcripts were decreased. Conclusion: These observations indicate that the circadian clock undergoes nutritional programming. The programming of the circadian clock may contribute to the alterations in feeding and energy metabolism associated with malnutrition in early life, which might promote the development of metabolic disorders in adulthood.