Corticotropin releasing factor (CRF) and leptin contributions to energy balance in genetically obese (lep-ob/lep-ob) mice, possible involvement of CRF in the leptin effects

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Yu, Bo Nancy
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Both corticotropin releasing factor (CRF), a central neuropeptide and initiating factor for adrenocorticortropic hormone and corticosterone, and leptin, the product of the 'OB' gene, which is absent in genetically obese 'lep'ob/'lep'ob mice, have similar effects on energy balance. Because of their shared anti-obesity effects and recent evidence that leptin coordinates central neuropeptide involvement in energy balance, three experiments were designed to investigate the possible involvement of CRF receptors in the central function of leptin in the genetic obesity of 'lep'ob/'lep 'ob mice: 'Study I' investigated the effects of leptin in mediating food intake, body weight, and thermogenesis of 'lep'ob/'lep'ob mice and the possible involvement of CRF receptors in leptin's function. Leptin (1.0 [mu]g/[mu]l/mouse) or vehicle [physiological saline (1 [mu]l)] was given intracerebroventricularly (ICV) 30 min after pretreatment of either vehicle or _-helical CRF [(10 [mu]g/[mu]l/mouse), a CRF antagonist] to genetically obese ('n' = 36) and lean ('n' = 25) mice. Food intake, water intake, and body weight were monitored at 2, 4, and 23 hr, and core body temperature (Tc) was recorded every 20-30 min for 4 hr and at 23 hr after drug treatments. Results indicated that leptin decreased cumulative food intake at 23 hr in 'lep'ob/'lep 'ob mice only. 'Study II' examined CRF's effects in mediating food-intake, body weight, and thermogenesis of mice. CRF (1.0 [mu]g/[mu]l/mouse) or vehicle was given ICV to obese ('n' = 31) and lean ('n' = 22) mice following the same pretreatments as in Study I. The same dependent variables were also measured. In contrast to leptin's effects in Study I, CRF had no significant effect on cumulative food intake, body weight change, or Tc in obese or lean mice. 'Study III' tested the possible involvement of CRF receptors in leptin's effect on oxygen consumption of mice. The 'lep'ob/' lep'ob mice ('N' = 19) were assigned to 1 of 3 treatment groups: vehicle - leptin, _-helical CRF - vehicle, _-helical CRF - leptin. Leptin and _- helical CRF doses were the same as in Studies I and II. Oxygen consumption was recorded via indirect calorimetry every 5-10 min for 1 hr after drug treatments. Leptin did not affect oxygen consumption in obese mice within 1 hr, but tended to stimulate oxygen consumption at 60 min after injection. Taken together, these data provide increasing support for the effect of leptin on energy balance in 'lep' ob/'lep'ob mice. (Abstract shortened by UMI.)