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Neurobeachin, a Regulator of Synaptic Protein Targeting, Is Associated with Body Fat Mass and Feeding Behavior in Mice and Body-Mass Index in Humans

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Nbea-haploinsufficient mice develop higher body weight due to higher adipose tissue mass.

(A) Western blot analysis of whole brain demonstrates that Nbea protein expression in Nbea+/− mice is half of that in WT mice. The same blot was sequentially developed with anti-Nbea, anti-Lrba and anti-Cadherin. 1, ½ and ¼ indicate a dilution series of loaded protein. (B) Male and female Nbea+/− mice develop higher body mass than WT controls. From week 14 on we continuously detected a significant genotype effect on body mass in males and females combined (week 14–15 p<0.05, week 16–19 p<0.01, afterwards p<0.001). (C,D) qNMR scans of mice aged 6–22 weeks shows that increased body mass of Nbea+/− mice is caused by increased fat tissue mass (significant genotype effect in females between week 6–21, in males in week 13–16, linear model with body mass as covariate). (E) The in-out-difference between daily metabolizable energy and daily energy expenditure was significantly increased in Nbea+/− mice at the age of 8 weeks. (F) Plasma insulin and (G) leptin at 22 weeks of age were significantly increased in Nbea+/− mice. (H,I) High-fat feeding from age 14 weeks accelerates weight gain, more pronouncedly in Nbea+/− than in WT mice. * within males, +within females, P<0.05; ** within males, ++within females, P<0.01; *** within males, +++within females, P<0.001; error bars, ± SEM. In part H, all genotype differences were significant for males with at least P<0.05 (except weeks −2 and 7, n.s.) and for females with at least P<0.001 (except week −2, p<0.01).

Figure 1

doi: https://doi.org/10.1371/journal.pgen.1002568.g001