Search

Glucose metabolism in fish remains a controversial area of research as many fish species are traditionally considered glucose-intolerant. Although energy homeostasis remodeling has been observed in fish with inhibited fatty acid β-oxidation (FAO), the effects and mechanism of the remodeling caused by blocked glucose uptake remain poorly understood. In this study, we blocked glucose uptake by knocking out glut2 in zebrafish. Intriguingly, the complete lethality, found in Glut2 -null mice, was not observed in glut 2 -/- zebrafish. Approxiamately 30% of glut 2 -/- fish survived to adulthood and could reproduce. The maternal zygotic mutant glut2 (MZ glut2 ) fish exhibited growth retardation, decreased blood and tissue glucose levels, and low locomotion activity. The decreased pancreatic β-cell numbers and insulin expression, as well as liver insulin receptor a ( insra ), fatty acid synthesis ( chrebp, srebf1, fasn, fads2 , and scd ), triglyceride synthesis ( dgat1a ), and muscle mechanistic target of rapamycin kinase ( mtor ) of MZ glut2 zebrafish, suggest impaired insulin-dependent anabolic metabolism. Upregulated expression of lipolysis ( atgl and lpl ) and FAO genes ( cpt1aa and cpt1ab ) in the liver and proteolysis genes ( bckdk, glud1b , and murf1a ) in muscle were observed in the MZ glut2 zebrafish, as well as elevated levels of P-AMPK proteins in both the liver and muscle, indicating enhanced catabolic metabolism associated with AMPK signaling. In addition, decreased amino acids and elevated carnitines of the MZ glut2 zebrafish supported the decreased protein and lipid content of the whole fish. In summary, we found that blocked glucose uptake impaired insulin signaling-mediated anabolism via β-cell loss, while AMPK signaling-mediated catabolism was enhanced. These findings reveal the mechanism of energy homeostasis remodeling caused by blocked glucose uptake, which may be a potential strategy for adapting to low glucose levels., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xi, Zhai, Liu, Gong, Lu, Zhang, Liu, Jin, Zhu, Yin, Xie and Han.)

High carbohydrate diet (HCD) causes metabolism disorder and intestinal damages in aquaculture fish. Berberine has been applied to improve obesity, diabetes and NAFLD. However, whether berberine contributes to the alleviation of HCD-induced intestinal damages in aquaculture fish is still unclear. Here we investigated the effects and mechanism of berberine on HCD-induced intestinal damages in largemouth bass ( Micropterus salmoides ). We found dietary berberine (50 mg/kg) improved the physical indexes (VSI and HSI) without affecting the growth performance and survival rate of largemouth bass. Importantly, the results showed that dietary berberine reduced the HCD-induced tissue damages and repaired the barrier in the intestine of largemouth bass. We observed dietary berberine significantly suppressed HCD-induced intestinal apoptosis rate (from 31.21 to 8.35%) and the activity level of Caspase3/9 ( P < 0.05) by alleviating the inflammation ( il1 β, il8 , tgf β, and IL-6, P < 0.05) and ER stress ( atf6 , xbp1 , perk , eif2 α, chopa , chopb , and BIP, P < 0.05) in largemouth bass. Further results showed that dietary berberine declined the HCD-induced excessive lipogenesis (oil red O area, TG content, acaca , fasn , scd , ppar γ, and srebp1 , P < 0.05) and promoted the lipolysis ( hsl , lpl , cpt1a , and cpt2 , P < 0.05) via activating adenosine monophosphate-activated protein kinase (AMPK, P < 0.05) and inhibiting sterol regulatory element-binding protein 1 (SREBP1, P < 0.05) in the intestine of largemouth bass. Besides, we also found that dietary berberine significantly promoted the hepatic lipid catabolism ( hsl , lpl , cpt1a , and cpt2 , P < 0.05) and glycolysis ( pk and ira , P < 0.05) to reduce the systematic lipid deposition in largemouth bass fed with HCD. Therefore, we elucidated that 50 mg/kg dietary berberine alleviated HCD-induced intestinal damages and improved AMPK/SREBP1-mediated lipid metabolism in largemouth bass, and evaluated the feasibility for berberine as an aquafeed additive to enhance the intestinal function of aquaculture species., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gong, Lu, Liu, Xi, Zhang, Liu, Jin, Yang, Zhu, Xie and Han.)