Systems neuroscienceInduction of brain-derived neurotrophic factor by leptin in the ventromedial hypothalamus
Section snippets
Animals
Eight- to 10-week-old C57BL/6J male mice (Nihon SLC, Hamamatsu, Japan) were used in the present study. The mice were maintained on a 12-h light/dark schedule with lights on at 08:00 h and unlimited access to food and water. At all times, the experiments were performed under the control of the Animal Research Control Committee in accordance with the Guidelines for Animal Experiments of Wakayama Medical University, the Japanese Government Notification on Feeding and Safekeeping of Animals (No. 6)
Phosphorylation of STAT3 by i.v. administration of leptin in the hypothalamus
First, we examined phosphorylation of STAT3 by i.v. administration of leptin in the hypothalamus. As shown in Fig. 1, phosphorylation of STAT3 began to increase at 30 min, reached the peak at 60 min, and was still maintained high levels at 90 min (P<0.01 ANOVA).
Leptin-induced expression of BDNF mRNA in the hypothalamus
To examine the effect of i.v. administration of leptin on the expression of BDNF mRNA in the hypothalamus, we performed Northern blot analysis. Consistent with a previous study (Marmigere et al., 1998), two different transcripts for BDNF
Discussion
Several investigators have reported that i.v. administration of leptin induces phosphorylation of STAT3 in the hypothalamus (Vaisse et al 1996, McCowen et al 1998, Hosoi et al 2002). Consistent with their studies, we also observed that phosphorylation of STAT3 in the hypothalamus reached peak at 60 min after i.v. administration of leptin. In addition, the expression of BDNF mRNA was also increased by leptin in the hypothalamus, especially in the VMH. There are at least two possible mechanisms
Conclusion
In conclusion, our results indicate for the first time that i.v. administration of leptin induces the expression of BDNF in the hypothalamus. In addition, we proposed a novel pathway that leptin-induced BDNF may activate neurons in the VMH (autocrine) and DMH to regulate food intake and energy homeostasis.
Acknowledgments
This work was supported by Grant-in-Aid for Scientific Research on Priority Areas (C) Medical Genome Science from the Ministry of Education, Culture, Sports, Science and Technology (13204074), the grant provided by the Ichiro Kanehara Foundation, and a Research Grant on Priority Areas from Wakayama Medical University.
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2016, PeptidesCitation Excerpt :Low BDNF levels could then mediate the relative increase in body fat seen in these mice with gut microbiota at adulthood, rather than being a consequence of their comparatively high body fat. During food shortage or impaired nutritional uptake, BDNF decreases as a consequence of low leptin [26]. In conventionally raised mice, which have improved nutritional uptake, we have surprisingly observed a decrease in BDNF mRNA [56].