Polarized Canine Liver Organoid Monolayers Capture Features of Western Diet-Induced Hepatic Metabolic Remodeling Across Transcriptomic, Lipidomic, and Biogenic Amine Signatures

ABSTRACT: Liver responses to Western-diet (WD) exposure remain incompletely defined, partly because conventional rodent models and immortalized hepatic cell lines incompletely recapitulate species-specific features of liver biology. Here, we established polarized epithelial monolayers from canine liver organoids derived from healthy beagles and beagles exposed to a WD for 8 weeks. We then used this platform to characterize diet-induced hepatic remodeling and to explore differential responses to two SGLT2 inhibitors, dapagliflozin and bexagliflozin. The monolayers developed reproducible apical-basal polarity, with transepithelial electrical resistance (TEER) values of 123-335 Ω·cm2, enabling compartment-resolved sampling. Bulk transcriptomics, lipidomics, and biogenic amine profiling each independently separated WD-derived from healthy monolayers. Periodic acid-Schiff staining provided qualitative support for this diet-associated molecular signature, showing increased carbohydrate-rich material consistent with glycogen accumulation in WD-derived monolayers. By contrast, 24-hour apical exposure to dapagliflozin or bexagliflozin at 20 µM produced no detectable transcriptomic differences and only weak, context-dependent metabolomic separation, which was restricted to the apical compartment in the untargeted metabolomics dataset. These findings establish canine liver organoid-derived polarized monolayers as a tractable in vitro platform that captures WD-induced hepatic remodeling across transcriptomic, lipidomic, and biogenic amine readouts, while providing a foundation for future targeted studies of candidate interventions for diet-associated hepatic dysfunction.

ORGANISM(S): Canis lupus familiaris

PROVIDER: GSE349735 | GEO | 2026/10/08

REPOSITORIES: GEO