Dietary betulinic acid alleviates high carbohydrate diet-induced hepatic de novo lipogenesis through AMPK signaling and improves liver health in channel catfish (Ictalurus punctatus)

Abstract

A high carbohydrate diet (HCD) induced excessive hepatic de novo lipogenesis, which caused metabolic disorder and impaired the health of fish species. Betulinic acid (BA) has been applied to ameliorate fatty liver and anti-inflammatory in mammals. Here, we investigated the effects of dietary BA supplementation on HCD-induced hepatic de novo lipogenesis and liver health in channel catfish (Ictalurus punctatus). The catfish were fed with three diets: NCD (18 % carbohydrate), HCD (36 % carbohydrate), HCD+BA (36 % carbohydrate with 150 mg/kg BA). After an 8-week feeding trial, we found that dietary BA decreased hepatosomatic index (HSI) and condition factor (CF) without affecting the growth of channel catfish fed HCD. Dietary BA significantly reduced the HCD-induced excessive lipid accumulation (oil red O area, TG content, and de novo lipogenesis gene expression, P < 0.05). Moreover, we found that dietary BA prevented hepatic lipid accumulation via activating phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and inhibiting sterol regulatory element-binding protein 1 (SREBP1) (P < 0.05) in liver of channel catfish fed HCD. Besides, we also found that dietary BA significantly prevented HCD-induced liver damage, as confirmed by liver H&E staining, reduced inflammation biomarkers (ALT, AST, hydroxyproline, α-sma and tgf-1β), downregulated expression of ER stress-related genes (eif2a, bip, atf4, xbp1) (P < 0.05). Overall, the present study indicated that dietary BA inclusion attenuated hepatic de novo lipogenesis, improved liver inflammation and reduced ER stress in channel catfish fed HCD.