C57BL/6J mice with a mutation in the obese (ob) gene are obese, diabetic, and exhibit reduced activity, metabolism, and body temperature. Daily intraperitoneal injection of these mice with recombinant OB protein lowered their body weight, percent body fat, food intake, and serum concentrations of glucose and insulin. In addition, metabolic rate, body temperature, and activity levels were increased by this treatment. None of these parameters was altered beyond the level observed in lean controls, suggesting that the OB protein normalized the metabolic status of the ob/ob mice. Lean animals injected with OB protein maintained a smaller weight loss throughout the 28-day study and showed no changes in any of the metabolic parameters. These data suggest that the OB protein regulates body weight and fat deposition through effects on metabolism and appetite.
The role of estradiol in mediating leptin’s effects on body weight was assessed in ovariectomized (OVX) mice before and after the onset of obesity. Ovariectomy did not alter leptin levels before the onset of obesity, and estradiol adminstration (0.05–17 μg/day for 14 days) did not significantly alter leptin levels if they were corrected for the estradiol-induced reduction in body fat. The converse was also true, in that leptin administration (0.4–140 μg/day) did not alter estradiol levels in intact mice. Furthermore, neither estradiol reduction (via ovariectomy) nor addition (via exogenous administration) significantly altered leptin’s ability to reduce fat mass. Leptin was equally effective in reducing body weight in lean or obese OVX mice and intact controls. Finally, estradiol did not change the magnitude of leptin’s effect on fat mass reduction when it was given in combination with leptin to lean intact or OVX mice. Estradiol may have indirectly affected leptin efficacy, because leptin did not produce as large a change in fat mass at lower doses in lean OVX mice as it did in intact counterparts. Taken together, these data suggested that 1) estradiol does not directly regulate leptin secretion or its effects on fat mass and 2) leptin does not directly regulate estradiol secretion or its effects on fat mass. Leptin and estradiol, however, may interact in an indirect fashion to affect fat utilization.
The thermic effect of 1.67 MJ (400 kcal) of carbohydrate (glucose), fat, protein and mixed meal were examined in 11 lean and 11 obese subjects by indirect calorimetry. The changes in metabolic rate in response over 90 min period (30-120 min after the meal) to the different meals were compared with that seen after a similar volume of low calorie drink. The thermic effects of glucose and protein were not significantly different between lean and obese subjects. Obese subjects showed very little increase in metabolic rate following ingestion of fat (-0.9 +/- 2.0%, mean +/- SEM) and this was significantly different from that seen in lean subjects (14.4 +/- 3.4%). The thermogenic response to mixed meal was also significantly lower in obese subjects when expressed as percentage change (12.9 +/- 2.3% compared to 25.0 +/- 4.8%). There was no evidence for delay in gastric emptying times for glucose and fatty meal in the six obese subjects in whom these were measured. We conclude that obese subjects show a reduced thermogenic response to fat.
This study examined graduate students’ desired and experienced levels of connectivity in an online, asynchronous distance degree program. Graduate students enrolled in the Masters of Science in Special Education distance degree program at a Midwest university were surveyed on both desired and experienced connectivity to their program, students, instructors, and advisors. Overall, student’s desired and experienced high connectivity to the program, their advisors, and their instructors; experiencing and wanting less connectivity to their fellow students. Specifically, three significant findings were noted: (1) students wanted high connectivity overall, with greatest connectivity desired with advisors and less connectivity wanted with other students; (2) there was variation among age cohorts and wanted connectivity with peers, advisors, instructors, and the program with statistically significant differences with regard to instructors, and other students; and (3) students experienced high connectivity. The relationships between graduate online learners and their instructors and advisors were correlated with the level of connectivity students experienced with their program. It was not as important to foster high connectivity among peers in the online learning environment. Further study should compare desired and wanted connectivity between departments, and across other universities to determine variables that may influence connectivity, and to identify best practices.
Spatial learning rate was compared in cognitively impaired aged rats infused with either brain-derived neurotrophic factor (BDNF) or nerve growth factor (NGF). BDNF or NGF was infused into the dorsal hippocampus/third ventricle while animals were being trained on the Morris water maze. Training continued until all rats met a spatial learning criterion. Seven weeks later, they were tested for retention of the task, and sacrificed for assessment of hippocampal high-affinity choline uptake (HACU) or hypothalamic biogenic amine levels. NGF, but not BDNF, improved spatial learning rate in aged rats and increased hippocampal choline uptake weeks after withdrawal of NGF. Although BDNF did not improve spatial learning, it did induce a partial, long-term normalization of the elevated hypothalamic 5-HT levels observed in our aged rats. These data suggest that (1) intrahippocampal/intraventricular infusion of NGF can improve the learning rate of aged, spatial learning-impaired rats, and that this improvement in acquisition could be associated with increased hippocampal cholinergic activity, and (2) that the BDNF-induced normalization of hypothalamic 5-HT levels in aged rats was not sufficient to improve learning rate in aged, spatial learning-impaired rats.
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