Session: MON 685-694-Mechanisms of Obesity
Poster Board MON-692
Methods: To determine the role of specific Bdnf promoters in energy homeostasis, we studied C57BL/6J mice in which promoters I, IV, or VI have been disrupted by insertion of a GFP-STOP cassette. Body weight was measured weekly in homozygous male Bdnf-I-/-, Bdnf-IV-/-, and Bdnf-VI-/- mice and wild-type (WT) littermates, which were fed ad libitum regular chow diet from weaning. Percent body fat was measured by MRI.
Results: Bdnf-I-/- mice (n=9) compared to WT littermates (n=7) had similar body weight at 8 weeks (mean ± SEM, Bdnf-I-/- vs. WT: 26.0 ± 0.7 vs. 25.7 ± 0.7 g, p=0.82), but significantly higher body weight by 12 weeks (33.8 ± 1.4 vs. 28.5 ± 0.6 g, p=0.009), which was even more pronounced at 6 months (49.4 ± 1.3 vs. 33.6 ± 0.9 g, p<0.0001) and associated with greater percent body fat (30.2 ± 3.2 vs. 16.8 ± 1.9%. p=0.02). In contrast, Bdnf-IV-/- mice (n=9) compared to WT littermates (n=8) had similar body weight at 6 months (Bdnf-IV-/- vs. WT: 34.4 ± 0.7 vs. 32.7 ± 0.6 g, p=0.12). Furthermore, Bdnf-VI-/- mice (n=10) compared to WT littermates (n=10) also had similar body weight at 6 months (Bdnf-VI-/-vs. WT: 29.2 ± 0.6 vs. 30.1 ± 0.4 g, p=0.23).
Conclusions: Mice lacking BDNF protein translated from transcripts driven by Bdnf promoter I had approximately 50% greater body weight and nearly 2-fold higher percent body fat compared to wild-type littermates at 6 months of age, whereas disruption of promoters IV or VI had no significant effect on body weight. Our findings suggest that Bdnf promoter I plays a critical role in regulating energy balance. Further studies are currently underway examining energy intake and expenditure, body composition, biochemical profile, and glucose homeostasis in these mice.
Disclosure: BL: Employee, GlaxoSmithKline. Nothing to Disclose: GIP, DJ, DM, OG, LT, KM, JCH
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