Effects Of The Intrauterine Growth Retardation (Iugr) Condition On Central Homeostatic Systems Regulating Energy Metabolism In Immediate Postnatal Life In The Sheep.

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Obesity has detrimental effects beyond wellbeing, increasing susceptibility to metabolic and cardiovascular diseases. Multiple factors like, genetics, calorie-dense foods, physical activity and social environment contribute to its development. In the last decades, epidemiological and clinical research has revealed associations between perinatal events and propensity to develop obesity in adult life. In particular intrauterine growth retardation (IUGR) has been associated with young and adult obesity and metabolic diseases. The IUGR condition induces accelerated growth, hyperphagia and obesity in rodents offered high caloric diets after birth. It has been discovered that hypothalamic regulation of energy homeostasis is defective in these animals due to an abnormal leptin profile during the first 2 postnatal weeks. During this period, leptin stimulates the development of axonal projections between various hypothalamic centers. However, the ontogeny of this phenomenon is different between altricial rodents and precocial species such as humans and sheep. Therefore, we used sheep to study the effects of the IUGR condition and high fat diets on immediate postnatal energy metabolism. We confirmed that IUGR and normal lambs display similar intake relative to their metabolic size, however, they accrete excess fat when compared on similar body weight. Our observations indicate that interactions between birth size and diet alter energy expenditure and retention through changes in thyroid hormones. Second, we iii evaluated the functionality of the melanocortin system, the best known mechanism of central control of energy intake and expenditure, and its effects on IUGR lambs. Using a melanocortin receptor agonist, we confirmed that this system is functional as early as postnatal day 4 in IUGR and its stimulation reduces adiposity by decreasing appetite and, presumably, increasing energy expenditure. Finally, we examined the role of leptin signaling during early life in the control of energy homeostasis and programming of future metabolic alterations and obesity. We discovered that treatment with a longlasting leptin antagonist during the first two weeks of life acutely increases appetite and growth but has no long-term effects on appetite, growth or body composition. iv

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IUGR; sheep; melanocortin; leptin; energy homeostasis; hypothalamus; intake; obesity; high-fat diet


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Union Local


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Boisclair, Yves R

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Bauman, Dale Elton
Van Amburgh, Michael E
Qi, Ling

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Animal Science

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Ph. D., Animal Science

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Doctor of Philosophy

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Government Document




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dissertation or thesis

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