Alcohol exposure in utero, even at doses that are not overtly teratogenic, persists as a major medical problem in this country. This proposal will establish both the mechanism and consequences of alcohol-induced damage to thermoregulation. An alcohol-exposed infant with body temperature disturbances is an infant at greater risk for respiratory distress, sudden infant death syndrome, and delayed neural growth. This alcohol-exposed infant may also be less responsive and thus may not be able to elicit adequate parental care as well as a non-exposed newborn. The alcohol- exposed newborn may need special care in terms of thermoregulation; a premature or low birth weight infant would be particularly at risk. This application will investigate the effects of prenatal alcohol exposure on the development of thermogenesis in brown adipose tissue, the primary means of heat production in infants. To determine how prenatal alcohol exposure alters the normal developmental course of sympathetic nervous system control of brown adipose tissue thermogenesis, this grant will examine the effects of prenatal alcohol exposure on the responsiveness of adrenergic receptors and the expression of ~3-adrenergic receptor mRNA in brown adipose tissue. Since the local production of thyroid hormone in brown adipose tissue also appears to be critical for thermogenesis, this grant will investigate the effects of prenatal alcohol exposure on the gestational surge in thyroid hormone production, when it functions as a developmental factor, and the postnatal production of thyroid hormone, when it functions as a """"""""permissive"""""""" agent to maximize tissue response to norepinephrine. Finally, this grant will determine whether the effects of prenatal alcohol exposure on control of brown adipose tissue function have longterm consequences in adult offspring. Brown adipose tissue thermogenesis is """"""""recruited"""""""" under two conditions that are physiologically stressful: high fat, high carbohydrate diets, and chronic exposure to cold. This grant will elucidate the effects of prenatal alcohol exposure on sympathetic nervous system regulation of diet-induced thermogenesis and cold-induced thermogenesis in brown adipose tissue of adult offspring, and determine if there are sex differences in response to these stressors. Since the early postpartum days represent an optimal intervention period, the information gained in this proposal will be of great value for early treatment and intervention. The studies on adult offspring will provide information about FAE populations at special risk: Native American living in northern climates, Alaskan Native Americans and older affected offspring with high fat/high carbohydrate diets.
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