UM-164 alleviates high starch diet-induced hepatic abnormal lipid accumulation via inhibiting pentose phosphate pathway and mTOR-SREBPs signaling in channel catfish (Ictalurus punctatus)

作者：Qisheng Lu, Xiaochen Ma, Guoli Han, Jinglu Jia, Jingyue Cao, Haokun Liu, Junyan Jin, Zhimin Zhang, Yunxia Yang, Xiaoming Zhu, Shouqi Xie, Dong Han · 发表于：Aquaculture Reports · 年份：2025 · DOI：10.1016/j.aqrep.2025.103031 · 被引用次数：2 · 研究领域：Liver Disease Diagnosis and Treatment、Diet, Metabolism, and Disease、Lipid metabolism and biosynthesis

High carbohydrate diet (HCD) has been shown to disrupt hepatic glycolipid metabolism and contribute to the development of metabolic dysfunction-associated steatotic liver disease (MASLD). However, effective therapeutic strategies targeting the underlying pathological mechanisms remain limited. Here, we designed a series of feeding experiments to evaluate the effects of dietary c-SRC inhibitor (UM-164) on glycolipid metabolism and liver health in channel catfish ( Ictalurus punctatus ) fed HCD. The experimental design consisted of three isonitrogenous and isolipidic diets: CON (18 % corn starch), HCD (36 % corn starch), and HCS (36 % corn starch; 20 mg/kg UM-164). Juvenile channel catfish (7.63 ± 0.02 g) were fed with these diets for 8 weeks. Our results revealed that the HCS treatment mitigated the HCD-induced increases in hyperglycemia, hyperlipidemia and glycosylated hemoglobin (GHb). HCS reduced the HCD-induced upregulation of pentose phosphate pathway (PPP)-related genes ( c-src , g6pd and 6pgd ), NADPH levels and glycolytic genes ( hk1 , gk , pfkla , pfklb and pk ). HCS reduced liver glycogen content by inhibiting the expression of PPP1R3G. HCS attenuated the HCD-induced activation of mTOR, leading to reduced expression of key lipid synthesis factors (SREBPs), as confirmed in vivo and vitro experiments. HCD resulted in a significant elevation of liver health indicators (ALT and AST), and UM-164 alleviated the HCD-induced liver damage. In conclusion, UM-164 reduced HCD-in...