20.500.12556/DKUM-98154 Chestnut-derived ellagitannins (FT50) protect against western diet-induced metabolic dysfunction and preserve beta cell function in mice Background: Western diet (WD) consumption accelerates the development of metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM). This study investigated whether chestnut-derived ellagitannins (FT50) modulate early metabolic alterations associated with WD feeding in C57BL/6J male mice. Methods: Male C57BL/6J mice were fed either a western diet (WD) or a WD supplemented with chestnut extract (FT50) for 12 weeks. Body weight, adiposity, glucose tolerance, and indices of insulin action were monitored throughout the study. Glucose and insulin homeostasis were assessed by measuring fasting glucose levels, insulin levels, and the HOMA-IR index. Pancreatic function was evaluated by ex vivo Ca2+ imaging in pancreas tissue slices to assess beta cell activation dynamics and islet network coordination. Results: WD feeding induced significant body weight gain, adiposity, hyperglycemia, glucose intolerance, changes consistent with impaired insulin action, and partially compensatory hyperinsulinemia. Supplementation with FT50 prevented weight gain and fat accumulation, reduced organ hypertrophy, and was associated with improved glucose and insulin-related parameters without affecting the caloric intake. FT50-fed mice showed improved glucose tolerance from week 4 onward, accompanied by a lower HOMA-IR values and reduced hyperinsulinemia, consistent with improved indirect markers of insulin action relative to WD-fed mice. Ex vivo Ca2+ imaging in pancreas tissue slices revealed that in FT50-fed mice, beta cells have higher activation thresholds, longer activation delays, and lower Ca2+ activity during the plateau phase, while their network coordination is preserved. Conclusions: In sum, these effects indicate reduced beta cell excitability and are consistent with an attenuation of early metabolic alterations under WD conditions. Overall, these findings suggest that FT50 supplementation modulates early WD-induced metabolic changes in male mice. However, the study is limited to early-stage alterations, does not address later stages of metabolic disease, and does not establish direct effects on insulin sensitivity. Within these constraints, chestnut extract represents a potentially promising bioactive dietary intervention for modulating early metabolic responses to WD. beta cells calcium imaging ellagitannins glucose intolerance insulin resistance metabolic syndrome mouse model western diet true true true Frontiers Angleški jezik Angleški jezik Znanstveno delo 2026-05-21 03:07:44 2026-05-21 13:24:52 2026-05-22 03:16:12 0000-00-00 00:00:00 2026 0 0 str. 1-18 Apr. 2026 Letn. 17 Apr. 2026 0000-00-00 Zaloznikova Objavljeno apc 2026-04-02 2026-04-08 2026-04-30 612.349.7 278686211 10.3389/fendo.2026.1802808 1664-2392 RAZ_Skelin_Masa_2026.pdf RAZ_Skelin_Masa_2026.pdf 1 8B79A79817C9A2FFDBD9E5B4613EDEB0 0b565ac0d92d53bbaf8e772a3f2d9b709a993df59ab0ea33b9bfab7841926674 2335de9c-5507-11f1-80bc-00155d580e34 https://dk.um.si/Dokument.php?lang=slv&id=206310 https://doi.org/10.3389/fendo.2026.1802808 0 4cbe0e04-5507-11f1-80bc-00155d580e34 https://dk.um.si/Dokument.php?lang=slv&id=206311 https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2026.1802808/full 1 7a15fba0-54b1-11f1-80bc-00155d580e34 https://dk.um.si/Dokument.php?lang=slv&id=206282 Medicinska fakulteta 0 0 0