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Hepatic lipid metabolism disorder due to excessive fat accumulation in fish is a significant problem in aquaculture. Studies have shown that grape seed procyanidin extract (GSPE) can regulate fish lipid metabolism and improve fish immunity. However, the mechanism is unclear. In this study, we used grass carp that stores excess fat in the liver as a model. In vitro, GSPE treatment of hepatocytes for 3 h significantly decreased TG content, accompanied with decreased expression of SREBP-1c, FAS, and ACC and increased expression of PPARα, ATGL, and LPL. GSPE treatment for 1 h significantly decreased expression of pro-inflammatory cytokines (TNFα, IL-6, IL-1β, and NF-κB) and increased the expression of anti-inflammatory cytokines (IL-10 and TGF-β1). In vivo, the administration of GSPE significantly reduced high-fat diet-induced increase of serum CHOL, TG, and HDL, but increased LDL content. GSPE treatment for 3 h increased expression of ATGL and LPL, and significantly decreased the expression of HFD-fed-induced SREBP-1c, ACC, FAS, PPARγ, PPARα, and H-FABP. GSPE treatment for 3 h also significantly decreased the expression of pro-inflammatory cytokines (TNFα, IL-6, and IL-1β) and increased the expression of the anti-inflammatory cytokine IL-10. The expression levels of the lipogenic miRNAs, miR-33, and miR-122, were suppressed both in vivo and in vitro by GSPE. In summary, GSPE had hypolipidemic and potential anti-inflammatory effects in the liver, potentially mediated by miR-33 and miR-122.

The present study was conducted to determine the effects of waterborne copper exposure on the lipid metabolism and intestinal microbiota of juvenile common carp (Cyprinus carpio L.). Common carp were exposed to four waterborne copper (Cu) concentrations (0 (control), 0.07 (low), 0.14 (medium), and 0.28 (high) mg Cu/L) for 8 weeks. Exposure to a high concentration of Cu had a negative effect on growth indices (weight gain rate (WGR) and specific growth rate (SGR)). The biochemical indices measured in serum (low-density lipoprotein (LDL) and triglycerides (TGs)) were significantly affected by exposure to medium concentration levels of Cu. The mRNA levels of lipogenic enzymes (acetyl-CoA carboxylase 1 (ACC-1) and fatty acid synthase (FAS)) and sterol-regulator element-binding protein-1 (SREBP-1) in liver tissue and tight binding protein genes (ZO-1 and occludin) in intestinal epithelial tissue were significantly downregulated in the 0.14 and 0.28 mg/L Cu treatment groups, accompanied by upregulated mRNA levels of lipolysis enzymes (lipoprotein lipase (LPL) and carnitine palmitoyl transferase 1 (CPT-1)) in the liver. The data also showed that the composition of intestinal microbiota was changed following Cu exposure and could alter the α-diversity and β-diversity. The abundances of few putative short-chain fatty acid (SCFA)-producing bacteria, including Allobaculum, Blautia, Coprococcus, Faecalibacterium, Roseburia, and Ruminococcus, decreased significantly. More specifically, Roseburia sequences were positively associated with lipogenic enzymes, total protein (TP), and TGs and negatively associated with lipolysis enzymes. Other sequences related to probiotics (Lactobacillus, Bacillus and Akkermansia) were also found to decrease, accompanied by an increase in sequences related to pathogens (Pseudomonas and Acinetobacter). To the best of our knowledge, the present study provides the first evidence that waterborne, chronic Cu exposure can disturb the composition of intestinal microbiota related to lipid metabolism and immunity in freshwater fish, thereby increasing the risk of pathogen invasion., (Copyright © 2018 Elsevier Inc. All rights reserved.)

To explore the mechanism of fatty liver formation induced by high non-protein energy diets in grass carp ( Ctenopharyngodon idella), basal diet and high-energy diets were fed to juvenile grass carp for 9 weeks. The experimental groups fed on high-energy diets which included a high-lipid diet (H- LIP), a high-carbohydrate diet (H- CHO) and a high-lipid and carbohydrate diet (H- CL). The control group fed on basal diet. Growth performance, liver fat accumulation, serum biochemical indexes and the expression levels of lipid metabolism-related genes ( SREBP-1, PPARγ, FAS, ACC1, and LPL) and mi RNAs (miR-33, miR-122, and miR-370) were examined at the end of the feeding trial. There were no significant differences in growth rate and feed efficiency among the four groups. However, significant increase in mesenteric and liver fat contents, and lipid droplets in the liver was induced by high-lipid and high-carbohydrate diets. There were significant differences in serum biochemical indicators such as AST/ ALT, GLB, TG and TP, and liver fatty acid composition between the control and experimental groups. The expression levels of SREBP-1, PPARγ, FAS, ACC1 and LPL were upregulated, while CPT-1 was downregulated with the high-energy treatments. Additionally, the expression levels of miR-33, miR-122 and miR-370 in the liver were higher in the three high-energy treatments than those in the control ( P < 0.05). The results suggest that modifications of lipid metabolism-related genes and mi RNAs may be involved in fatty liver formation induced by high non-protein energy diets in grass carp. [ABSTRACT FROM AUTHOR]