Fig. 7. Associations of RIMS1 with cognition in the validation cohort 3 and Rim overexpression in Drosophila fat body effects in learning and gene expression profiles.

(A and B) Scatter plots of the partial Spearman’s rank correlations (adjusted for age, BMI, sex, and education years) between the VAT expression levels of RIMS1 and the ROCF copy scores in (A) morbid obese patients (BMI > 35 kg/m²) and (B) patients with a BMI of <35 kg/m² from the ADIPOBRAIN cohort (n = 40). (C) Rim overexpression in the Drosophila fat body and associations with learning. Differences in CI between naïve and trained males were assessed with Kruskal-Wallis nonparametrical test and post hoc Dunn’s multiple comparison test. LIs to assess either short-term memory (for Vmat) or learning (for Rim) were calculated from CIs as specified in Materials and Methods. Statistical significance was determined with the nonparametrical bootstrap analysis with 10,000 replicates. ****P < 0.0001. (D) Rim relative expression assessed by quantitative RT-PCR (qRT-PCR) in fly brain or fat body in UAS-Rim fat body–specific overexpression flies and its corresponding genetic background control. Data are derived from a minimum of five biological and two technical replicates. (E) Dot plot of significantly (q < 0.1) overrepresented Reactome pathways, (F) GO biological processes (GO-BP), and (G) molecular functions (GO-MF) associated with the miss expressed genes in the fat body of UAS-Rim flies. (H and I) Gene-concept network depicting significant genes involved in enriched Reactome pathways [from (E)] and GO-GO-BP [from (F)]. (J) Overrepresentation analysis of pathways (q > 0.1) associated with differentially expressed gene transcript in UAS-Rim fly heads based on the Reactome database. (K) Gene-concept network associated with significant genes involved in Reactome pathways of (J). (L) Significantly overrepresented GO molecular functions of significant gene transcripts in fly heads (q > 0.1). HDL, high-density lipoprotein; HSF1, heat shock factor 1; IGF, insulin-like growth factor; IGFBP, insulin-like growth factor binding protein; NADP⁺, nicotinamide adenine dinucleotide phosphate; PCNA, proliferating cell nuclear antigen.