Carboxyl Ester Lipase Protects Against Metabolic Dysfunction-Associated Steatohepatitis by Binding to Fatty Acid Synthase

Carboxyl ester lipase(CEL),a pivotal enzyme involved in lipid metabolism,is recurrently mutated in obese mice.Here,we aimed to elucidate the functional significance,molecular mechanism,and therapeutic potential of CEL in metabolic dysfunction-associated steatohepatitis(MASH).Hepatocyte-specific carboxyl ester lipase gene(Cel)knockout(Cel^(DHEP))and wildtype(WT)littermates were fed with cholinedeficient high-fat diet(CD-HFD)for 16 weeks,or methionine-and choline-deficient diet(MCD)for three weeks to induce MASH.Liquid chromatography–mass spectrometry and co-immunoprecipitation were employed to identify the downstream targets of CEL.CD-HFD/MCD-fed WT mice received intravenous injections of CEL-adeno-associated viral,serotype 8(AAV8)to induce specific overexpression of CEL in the liver.We observed a decrease in CEL protein levels in MASH induced by CD-HFD or MCD in mice.Cel^(DHEP) mice fed with CD-HFD or MCD exhibited pronounced hepatic steatosis,inflammation,lipid peroxidation,and liver injury compared to WT littermates,accompanied by increased hepatic nuclear factor kappa-light-chain-enhancer of activated B cell(NF-jB)activation.Consistently,Cel knockdown in mouse primary hepatocytes and AML12 cells aggravated lipid accumulation and inflammation,whereas CEL overexpression exerted the opposite effect.Mechanistically,CEL directly bound to fatty acid synthase(FASN),resulting in reduced FASN SUMOylation,which in turn promoted FASN degradation through the proteasome pathway.Furthermore,inhibition of FASN ameliorated hepatocyte lipid accumulation and inflammation induced by Cel knockdown in vivo and in vitro.Hepatocyte-specific CEL overexpression using AAV8-Cel significantly mitigated steatohepatitis in mice fed with CD-HFD or MCD.CEL protects against steatohepatitis development by directly interacting with FASN and suppressing its expression for de novo lipogenesis.CEL overexpression confers a therapeutic benefit in steatohepatitis.

Research Progress in Phage

With excessive utilization of antibiotics in recent years,bacterial drug resistance problem is serious increasingly,and it is more and more difficult to develop anti-infective drug,while it does not have these problems to use phage controlling disease.Phage is a kind of prokaryotic virus,widely exists in the nature and includes bacteriophage,cyanophage and actinophage.Due to its potential of replacing antibiotics to treat disease,phage receives more and more attention.In this paper,based on development status of phage research at home and abroad,discovery process,naming method and classification basis of phage are introduced comprehensively,and advantages and limitations of phage applying in prevention and control of bacterial diseases are analyzed.We introduce application status of phage in human medicine,prevention and control of diseases for terrestrial animals and aquaculture,and the effects of phage in sewage treatment,prevention and control of microbial contamination of food and detection technology,and point out the shortages of phage in the above application.Meanwhile,we also discuss application prospects of phage in disease prevention and control,environmental protection and food safety.

Effects of solid-state fermentation product of yeast supplementation on liver and intestinal health,and resistance of common carp(Cyprinus carpio)against spring viraemia carp virus

This study aimed to investigate the effects of solid-state fermentation products of yeast(SFPY)on liver and intestinal health and disease resistance of common carp(Cyprinus carpio).A total of 200 common carp with an initial average weight of 2.55±0.004 g were divided into 5 groups(4 replications per group and 10 fish per replication),and were fed with one of five diets,including a control diet and 4 diets supplemented with 2‰(Y2),3‰(Y3),4‰(Y4),or 5‰(Y5)SFPY,respectively,for 8 weeks.Results indicated that,the addition of SFPY to the diet of common carp did not affect the growth performance or survival rate of fish(P=0.253).Interestingly,with the addition of SFPY,the triacylglycerol(TAG)content of the liver presented a linear decreasing tendency(P=0.004),with significantly decreased in Y4 and Y5 groups(P=0.035)compared with control.Serum lipopolysaccharide(LPS)content and diamine oxidase(DAO)activity presented a negative linear relationship with the addition of SFPY(P=0.015,P=0.030),while serum lipopolysaccharide binding protein(LBP)content first decreased and then increased(P<0.001).The total antioxidant capacity(T-AOC)in the intestine of fish increased continuously with increasing SFPY supplementation(P=0.026),reaching the highest level in Y5 group.The villus height in all experimental groups were significantly higher than that in the control group(P<0.001).Furthermore,compared to the control,adding 3‰SFPY to the control diet of common carp significantly increased the relative abundance of Fusobacteria(P=0.018)and decreased that of Proteobacteria(P=0.039)at phylum level,and increased the relative abundance of Cetobacterium(P=0.018)and decreased that of Shewanella(P=0.013)at genus level.Compared with the control,the relative mRNA expression level of spring viraemia of carp virus N protein(SVCV-n)in the kidney was lower than that of the control group without significance and bottomed out in Y4 group(P=0.138).In conclusion,dietary SFPY enhanced the SVCV resistance capacity of common carp by improving liver and intestinal health and modulating the gut microbiota.Thus,SFPY is a potential feed additive to be used in aquaculture to reduce the huge economic loss of common carp due to SVCV disease.Based on liver TAG content and intestinal villus height,the optimal addition level of SFPY was 3.02‰and 2.72‰,respectively.

Interactions between commensal bacteria and viral infection:insights for viral disease control in farmed animals

Viral diseases cause serious economic loss in farmed animals industry.However,the efficacy of remedies for viral infection in farmed animals is limited,and treatment strategies are generally lacking for aquatic animals.Interactions of commensal microbiota and viral infection have been studied in recent years,demonstrating a third player in the interaction between hosts and viruses.Here,we discuss recent developments in the research of interactions between commensal bacteria and viral infection,including both promotion and inhibition effect of commensal bacteria on viral pathogenesis,as well as the impact of viral infection on commensal microbiota.The antiviral effect of commensal bacteria is mostly achieved through priming or regulation of the host immune responses,involving differential microbial components and host signaling pathways,and gives rise to various antiviral probiotics.Moreover,we summarize studies related to the interaction between commensal bacteria and viral infection in farmed animals,including pigs,chickens,fish and invertebrate species.Further studies in this area will deepen our understanding of antiviral immunity of farmed animals in the context of commensal microbiota,and promote the development of novel strategies for treatment of viral diseases in farmed animals.