
Journal of Diabetes Research, Journal Year: 2025, Volume and Issue: 2025(1)
Published: Jan. 1, 2025
Background: Fat accumulation in the pancreas, known as nonalcoholic fatty pancreatic disease (NAFPD), is associated with obesity and may lead to prediabetes Type 2 diabetes. Reducing endoplasmic reticulum stress enhancing autophagy could offer therapeutic benefits. This study examines effects of fisetin (FSN) hydroxychloroquine (HCQ) on NAFPD. Method: Forty‐eight Male C57BL/6 J mice were assigned a standard chow diet (SCD) or high‐fat (HFD) for 16 weeks. The HFD group was divided into five subgroups; each contains eight mice: HFD, + V (vehicle), FSN, HCQ, FSN HCQ. given daily at 80 mg/kg, HCQ injected IP 50 mg/kg twice weekly more 8 Insulin resistance assessed through OGTT HOMA‐IR. Histological analysis tissue conducted, protein mRNA levels molecules ER using PCR immunoblotting techniques. Result: significantly reduced weight gain, adipocyte accumulation, insulin caused by obese mice, combination two compounds producing even pronounced effects. Additionally, increased expression UPR markers ATF4 CHOP, response that further intensified In contrast, attenuated regulating GRP78 levels. Furthermore, resulted significant decrease LC3II/LC3I ratio an p62 due p‐AMPK Following treatment these alterations reversed, leading decreased mTOR such ATG5 Beclin1. Conclusion: Our reveals effectively combat HFD‐induced NAFPD, improving sensitivity addressing fat deposition linked metabolic syndrome. While cause stress, offers protective effects, supporting their combined use better outcomes.
Language: Английский