AAV5-mediated manipulation of insulin expression in choroid plexus has long-term metabolic and behavioral consequences.

The choroid plexus (CP) is a source of trophic factors for the developing and mature brain. Insulin is produced in epithelial cells of the CP (EChPs), and its secretion is stimulated by Htr2c-mediated signaling. We modulated insulin expression in EChPs with intracerebroventricular injections of AAV5. Insulin overexpression in CP decelerates food intake, whereas its knockdown has the opposite effect. Insulin overexpression also results in reduced anxious behavior. Transcriptomic changes in the hypothalamus, especially in synapse-related processes, are also seen in mice overexpressing insulin in CP. Last, activation of Gq signaling in CP leads to acute Akt phosphorylation in neurons of the arcuate nucleus, indicating a direct action of CP-derived insulin on the hypothalamus. Taken together, our findings signify that CP is a relevant source of insulin in the central nervous system and that CP-derived insulin should be taken into consideration in future work pertaining to insulin actions in the brain.

Faith, Activity, and Nutrition Randomized Dissemination and Implementation Study: Countywide Adoption, Reach, and Effectiveness.

INTRODUCTION: Faith-based organizations can contribute to improving population health, but few dissemination and implementation studies exist. This paper reports countywide adoption, reach, and effectiveness from the Faith, Activity, and Nutrition dissemination and implementation study. DESIGN: This was a group-randomized trial. Data were collected in 2016. Statistical analyses were conducted in 2017. SETTING/PARTICIPANTS: Churches in a rural, medically underserved county in South Carolina were invited to enroll, and attendees of enrolled churches were invited to complete questionnaires (n=1,308 participated). INTERVENTION: Churches (n=59) were randomized to an intervention or control (delayed intervention) condition. Church committees attended training focused on creating opportunities, setting guidelines/policies, sharing messages, and engaging pastors for physical activity (PA) and healthy eating (HE). Churches also received 12 months of telephone-based technical assistance. Community health advisors provided the training and technical assistance. MAIN OUTCOMES MEASURES: The Reach, Efficacy/Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework guided measurement of adoption and reach. To assess effectiveness, church attendees completed post-test only questionnaires of perceptions of church environment, PA and fruit and vegetable (FV) self-efficacy, FV intake, and PA. Regression models controlled for church clustering and predominant race of congregation, as well as member age, gender, education, and self-reported cancer diagnosis. RESULTS: Church adoption was 42% (55/132). Estimated reach was 3,527, representing 42% of regular church attendees and 15% of county residents. Intervention church attendees reported greater church-level PA opportunities, PA and HE messages, and PA and HE pastor support (p<0.0001), but not FV opportunities (p=0.07). PA self-efficacy (p=0.07) and FV self-efficacy (p=0.21) were not significantly higher in attendees of intervention versus control churches. The proportion of inactive attendees was lower in intervention versus control churches (p=0.02). The proportion meeting FV (p=0.27) and PA guidelines (p=0.32) did not differ by group. CONCLUSIONS: This innovative dissemination and implementation study had high adoption and reach with favorable environmental impacts, positioning it for broader dissemination. TRIAL REGISTRATION: This study is registered at www.clinicaltrials.gov NCT02868866.