Verbascoside exerts an anti-atherosclerotic effect by regulating liver glycerophospholipid metabolism

Verbascoside,abundant in olive mill wastewater,is a phenylethanolic glycoside with a wide range of pharmacological activities.Atherosclerosis(AS)is a common metabolic disease and abnormal lipid metabolism in liver is inseparable from its formation and development.In this study,the anti-atherosclerotic effect of verbascoside was evaluated by establishing an atherosclerosis model based on western diet feeding of apolipoprotein E-defi cient mice for 16 weeks.After 12 weeks of administration during the feeding period,the levels of total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C)in the plasma of mice were signifi cantly decreased,the formation of arterial plaques was delayed,and the levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST)and lactate dehydrogenase(LDH)in plasma were alleviated,showing the hepatoprotective effect.In addition,based on untargeted lipidomic analysis,verbascoside stabilized glycerophospholipid metabolism,modulated lipid metabolism disorders and reduced lipid deposition in the liver to achieve the therapeutic effi cacy against atherosclerosis by regulating cardiolipin(CL),ether-linked phosphatidylcholine(ether-PC),lysophophatidylcholine(LPC),phosphatidylcholine(PC),oxidized phosphatidylcholine(OxPC),oxidized phosphatidylethanolamine(OxPE),triacylglycerol(TG),sphingomyelin(SM)back to normal levels.

Double-edged effect of sodium citrate in Nile tilapia(Oreochromis niloticus):Promoting lipid and protein deposition vs.causing hyperglycemia and insulin resistance

Citrate is an essential substrate for energy metabolism that plays critical roles in regulating glucose and lipid metabolic homeostasis.However,the action of citrate in regulating nutrient metabolism in fish remains poorly understood.Here,we investigated the effects of dietary sodium citrate on growth performance and systematic energy metabolism in juvenile Nile tilapia(Oreochromis niloticus).A total of 270Nile tilapia(2.81±0.01 g)were randomly divided into three groups(3 replicates per group,30 fish per replicate)and fed with control diet(35%protein and 6%lipid),2%and 4%sodium citrate diets,respectively,for 8 weeks.The results showed that sodium citrate exhibited no effect on growth performance(P>0.05).The whole-body crude protein,serum triglyceride and hepatic glycogen contents were significantly increased in the 4%sodium citrate group(P<0.05),but not in the 2%sodium citrate group(P>0.05).The 4%sodium citrate treatment significantly increased the serum glucose and insulin levels at the end of feeding trial and also in the glucose tolerance test(P<0.05).The 4%sodium citrate significantly enhanced the hepatic phosphofructokinase activity and inhibited the expression of pyruvate dehydrogenase kinase isozyme 2 and phosphor-pyruvate dehydrogenase E1 component subunit alpha proteins(P<0.05).Additionally,the 4%sodium citrate significantly increased hepatic triglyceride and acetyl-Co A levels,while the expressions of carnitine palmitoyl transferase 1a protein were significantly down-regulated by the 4%sodium citrate(P<0.05).Besides,the 4%sodium citrate induced crude protein deposition in muscle by activating m TOR signaling and inhibiting AMPK signaling(P<0.05).Furthermore,the 4%sodium citrate significantly suppressed serum aspartate aminotransferase and alanine aminotransferase activities,along with the lowered expression of pro-inflammatory genes,such as nfκb,tnfa and il8(P<0.05).Although the 4%sodium citrate significantly increased phosphor-nuclear factor-k B p65 protein expression(P<0.05),no significant tissue damage or inflammation occurred.Taken together,dietary supplementation of sodium citrate could exhibit a double-edged effect in Nile tilapia,with the positive aspect in promoting nutrient deposition and the negative aspect in causing hyperglycemia and insulin resistance.

Cloning, expression, and polymorphism of the ECI1 gene in various pig breeds

The enzyme △3,△2-dienoyl-CoA isomerase （ECI1） plays a crucial role in the mitochondria113-oxidation of fatty acids with a double-bond in odd and even positions. The ECll gene might be a qualified candidate for studies pertaining to lipid deposition and meat quality in swine. In the present study, ECI1 cDNA of the Tibetan pig was obtained by in silico cloning and verified by PCR analysis. Single-nucleotide polymorphisms （SNPs） of ECll were screened by PCR-sequencing and genotypes of those SNPs were tested by PCR-restriction fragment length polymorphism （PCR-RFLP） in Diannan small-ear pigs （DSP, n=40）, Tibetan pigs （TP, n=60） and Yorkshire pigs （YP, n=30）. The expression levels of ECll were analyzed by real-time quantitative PCR and Western blotting in tissues of the liver, backfat, and Iongissimus dorsi （LD） muscle of DSP （n=8）, TP （n=8） and YP （n=8）. Single factor linear correlation analysis was applied separately for each breed to evaluate correlations between ECll gene expression in the LD muscle and intramuscular fat （IMF） content. We obtained an ECll gene length of 1 401 bp from the cDNA that contained a full coding region of 909 bp. Three novel SNPs （g.42425337G〉A; g.42424666A〉G; and g.42422755A〉G） were detected, and only g.42424666A〉G exhibited three genotypes among the three breeds. The ECll expression levels in the LD muscle of DSP and TP were significantly higher than that of YP （P〈0.05）. Moreover, TP had the highest ECI1 expression in backfat （P〈O.01）, and a positive correlation was observed between gene expression and IMF content. The results suggest that differences in ECI1 gene expression might be related to lipid depo- sition and meat quality in pig.

Multi-omics analysis reveals gut microbiota-induced intramuscular fatdeposition via regulating expression of lipogenesis-associated genes

The gut microbiome has great effects on the digestion, absorption, and metabolism of lipids. However,the microbiota composition that can alter the fat deposition and the meat quality of pigs remains unclear.Here, we used Laiwu (LW) pigs (a native Chinese breed with higher intramuscular fat) compared withcommercial crossbreed Duroc×(Landrace×Yorkshire) (DLY) pigs to investigate the effects of microbiotaon meat quality, especially in intramuscular fat content. A total of 32 DLY piglets were randomly allottedto 4 groups and transplanted with fecal microbiota from healthy LW pigs. The results indicated that thehigh dose of fecal microbiota transplantation (HFMT) selectively enhanced fat deposition in longissimusdorsi (P < 0.05) but decreased backfat thickness (P < 0.05) compared with control group. HFMT significantlyaltered meat color and increased feed conversation ratio (P < 0.05). Furthermore, the multi-omicsanalysis revealed that Bacteroides uniformis, Sphaerochaeta globosa, Hydrogenoanaerobacterium saccharovorans,and Pyramidobacter piscolens are the core species which can regulate lipid deposition. A total of140 male SPF C57BL/6j mice were randomly allotted into 7 groups and administrated with these 4 microbesalone or consortium to validate the relationships between microbiota and lipid deposition.Inoculating the bacterial consortium into mice increased intramuscular fat content (P < 0.05) comparedwith control mice. Increased expressions of lipogenesis-associated genes including cluster of differentiation36 (Cd36), diacylglycerol O-acyltransferase 2 (Dgat2), and fatty acid synthase (FASN) wereobserved in skeletal muscle in the mice with mixed bacteria compared with control mice. Together, ourresults suggest that the gut microbiota may play an important role in regulating the lipid deposition in the muscle of pigs and mice.

The molecular pathogenic role of inflammatory stress in dysregulation of lipid homeostasis and hepatic steatosis

Non-alcoholic Fatty Liver Disease(NAFLD)is becoming the leading cause of chronic liver injury in developed countries and China.Chronic systemic inflammation plays a decisive role and is fundamental in the progression of NAFLD from simple steatosis(SS)toward higher risk nonalcoholic steatohepatitis(NASH)states.However,the exact mechanisms by which inflammation leading to NASH are incompletely understood.In this review,we focus the role of the cross talk between inflammation and lipid homeostasis on the progression of NAFLD.