Research
| Title： | 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) |
|---|---|
| First author： | Lu, Qisheng; Ma, Xiaochen; Han, Guoli; Jia, Jinglu; Cao, Jingyue; Liu, Haokun; Jin, Junyan; Zhang, Zhimin; Yang, Yunxia; Zhu, Xiaoming; Xie, Shouqi; Han, Dong |
| Journal： | AQUACULTURE REPORTS |
| Years： | 2025 |
| DOI： | 10.1016/j.aqrep.2025.103031 |
| Abstract： | 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-induced hepatic lipid accumulation by inhibiting PPP and mTOR-SREBPs signaling, thereby improving liver health. These findings suggest that UM-164 is a promising therapeutic agent for protecting liver health and may provide a viable basis for the treatment of MASLD. |
