Extended Data Fig. 6: mGIPR-Ab/P1 treatment and CNS GIPR KO result in gene expression profile changes in liver.

Transcriptomic analysis was conducted on liver tissues from Gipr^fl/fl, Gipr^Syn−/−, Glp1r^fl/fl and Glp1r^Wnt1−/− mice treated with either vehicle or mGIPR-Ab/P1. Samples were analyzed for differential gene expression (DEG) using DESeq2 and Ingenuity Pathway Analysis was used to identify most significantly affected pathways. Bubble plot representing pathways enriched for DEGs in (a) Gipr^Syn−/− vehicle-treated and Gipr^fl/fl mGIPR-Ab/P1-treated mice, and (c) Glp1r^Wnt1−/− vehicle-treated and Glp1r^fl/fl mGIPR-Ab/P1-treated mice. Size of bubble represent p-value and color shade of bubble represent z-score/enrichment score for each pathway. Heat map for top 5 genes per enriched pathway in (b) Gipr^Syn−/− vehicle-treated and Gipr^fl/fl mGIPR-Ab/P1-treated mice, and (d) Glp1r^Wnt1−/− vehicle-treated and Glp1r^fl/fl mGIPR-Ab/P1-treated mice. Top 5 genes were selected based off biological relevance and statistical significance. (A,C) Right-tailed Fisher’s Exact Test. n=5/group. Chrom = chromosomal, activat. = activation, metab. = metabolism, superpath. = superpathway, biosyn. = biosynthesis.

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