DESCRIPTION (Scanned from the Applicant's Description): The long-term goal of this project is to determine how environmental exposures during development contribute to the acquisition of obese or hypertensive traits in the adult. If successful, it may be possible to devise strategies for early intervention which might prevent or at least forestall the development of these disorders. The studies proposed in this application address the lasting influence of several environmental factors during fetal and neonatal life (environmental temperature, maternal diet and prenatal exposure to glucocorticoids) on an animal's susceptibility to become obese as an adult. It is the contention of the applicants that these three exposures induce different obesity-prone phenotypes by altering specific aspects of sympathoadrenal function, along with possible increases in food intake. The applicants propose that early exposure to cool environmental temperatures will predispose animals to develop obesity without features of the so-called 'metabolic syndrome', while maternal ingestion of a synthetic diet will predispose similar animals to develop obesity along with the 'metabolic syndrome'. The applicants also predict that prenatal exposure to glucocorticoids will exacerbate any other tendencies in the offspring to develop the 'metabolic syndrome' in conjunction with obesity. Furthermore, since these exposures are not mutually exclusive of one another, the applicants propose that maternal exposure both to glucocorticoids and to a synthetic diet will interact synergistically to exaggerate tendencies in the offspring toward obesity and the 'metabolic syndrome'. In addition, since the brainstem locus for sympathetic premotoneurons to brown fat in raphe pallidus (RPa) may also contribute to regulation of glucose metabolism, it is hypothesized that activation or inhibition of RPa will produce corresponding changes in glucose disposal. The applicants propose to use techniques of norepinephrine (NE) turnover and urine catecholamine levels to assess sympathetic and adrenal medullary function, respectively, in unanesthetized animals and to utilize neurophysiological studies of impulse traffic in sympathetic fibers of anesthetized rats to examine the importance of RPa in mediating SNS activation by specific stimuli, such as insulin and leptin. The potential impact of changes in sympathetic activity regulated by RPa for glucose and energy metabolism will also be examined.
|Effective start/end date||4/15/01 → 2/28/06|
- National Institute of Diabetes, Digestive and Kidney Diseases (5 R01 DK020378-26)