Advances in studies on ACSL1’s promoting hepatic lipid accumulation and inflammation and participating in disease development / 西安交通大学学报(医学版)

The acyl-CoA synthetase long-chain (ACSL) belongs to an enzyme encoded by a polygenic family. ACSL, located in the endoplasmic reticulum and outer mitochondrial membrane, can catalyze fatty acids to form acyl-CoA, participating in many physiological processes, such as fatty acid metabolism and membrane modification. The ACSL family plays different roles in the fatty acid metabolism of different cells, and its dysfunction can lead to conditions such as fatty liver, arteriosclerosis, and diabetes. As a major subtype of the ACSL family in the liver, ACSL family member 1 (ACSL1) is mainly involved in the maintenance of cholesterol stability, fatty acid activation, and bile acid metabolism. It is also associated with the development of certain liver diseases such as hepatocellular carcinoma and steatosis. This paper reviews differences in physiological functions and functional characteristics of ACSL family members. It also discusses the advances in studies on the role of ACSL1 in influencing lipid metabolism, regulating cellular iron death, and the development of related diseases such as liver fibrosis, hepatocellular carcinoma, cachexia, steatosis, thyroid cancer, and breast cancer.

ACSL5, a prognostic factor in acute myeloid leukemia, modulates the activity of Wnt/β-catenin signaling by palmitoylation modification / 医学前沿

Acyl-CoA synthetase long chain family member 5 (ACSL5), is a member of the acyl-CoA synthetases (ACSs) family that activates long chain fatty acids by catalyzing the synthesis of fatty acyl-CoAs. The dysregulation of ACSL5 has been reported in some cancers, such as glioma and colon cancers. However, little is known about the role of ACSL5 in acute myeloid leukemia (AML). We found that the expression of ACSL5 was higher in bone marrow cells from AML patients compared with that from healthy donors. ACSL5 level could serve as an independent prognostic predictor of the overall survival of AML patients. In AML cells, the ACSL5 knockdown inhibited cell growth both in vitro and in vivo. Mechanistically, the knockdown of ACSL5 suppressed the activation of the Wnt/β-catenin pathway by suppressing the palmitoylation modification of Wnt3a. Additionally, triacsin c, a pan-ACS family inhibitor, inhibited cell growth and robustly induced cell apoptosis when combined with ABT-199, the FDA approved BCL-2 inhibitor for AML therapy. Our results indicate that ACSL5 is a potential prognosis marker for AML and a promising pharmacological target for the treatment of molecularly stratified AML.

Study on the improvement effect of Ginsenoside Rg1 on nonalcoholic fatty liver phenotype by regulation ofβ-oxidation / 重庆医学

Objective To investigate the role of Ginsenosides Rg1 for non-alcoholic fatty liver disease by β-oxidation.Methods 120 SD rats were randomly divided into control group(CON),model group(HFD),Ginsenosides Rg1low,medium and high dose group (GLD ,GMD and GHD) ,sodium deoxycholate of bear treatment group (PDT ) ,20 rats in each group .After 4 and 8 weeks treatment ,the rats were sacrificed ,Pathology of hepatic tissue was tested by HE staining ,and liver function ,lipid levels ,hepatic ac-yl-CoA synthetase (CoASH1) ,carnitine acyl transferase I(CATI) and acetyl coenzyme A oxidase 1 (ACOX1) mRNA and protein expression were tested .Results After 4 weeks of treatment ,the liver function tested by HE staining only improved in GHD group . After 8 weeks ,there′s a little fat particles aggregation in PDT and GLD groups ,but no infiltration of fat in GMD and GHD groups . After 4 weeks ,AST ,ALT and AKP ,CHOL ,TG and LDL-C levels were significantly lower in PDT ,GLD ,GMD and GHD groups compared with HFD group (P<0 .05) ,which were significant declined 8 weeks later .After 4 weeks ,HDL-C level in four groups was significantly increased ,then reached the normal level 8 weeks later .After 4 weeks ,CoASH1 ,CATI and ACOX1 expressions in hepatic tissue of four groups were significantly increased ,which improved more obviously after eight weeks .Conclusion Ginsen-oside Rg1 can improves nonalcoholic fatty liver phenotype by regulation of β-oxidation .

Ginsenoside Rg1 improves liver function by regulating fat metabolism in rats with non-alcoholic fatty liver disease / 中国病理生理杂志

AIM:To investigate whether ginsenoside Rg1 attenuates high-fat diet ( HFD)-induced non-alcoho-lic fatty liver disease ( NAFLD) by improving β-oxidation.METHODS: SD rats ( n=60) were randomly divided into control group ( CON ) , HFD group, low-dose, medium-dose and high-dose ginsenoside Rg1 groups ( LDG, MDG and HDG) and positive drug ( sodium ursodeoxycholate) treatment group ( PDT) .High-fat diet was given for 8 weeks to suc-cessfully establish an NAFLD model.The animals were treated with the appropriate medications for 4 weeks and 8 weeks af-ter modeling, and sacrificed to collect the liver tissues for observing the pathologic changes with HE staining and for detec-ting liver functions and lipid levels.The expression of hepatic acyl-CoA synthetase 1 (CoASH1), carnitine acyltransferase I (CATI) and acyl-CoA oxidase 1 (ACOX1) at mRNA and protein levels was determined by RT-PCR and Western blot-ting.RESULTS:After 4-week treatment, the fatty infiltration of the liver tissues in PDT group, LDG group and MDG group was not attenuated except HDG group.After 8 weeks of treatment, a small number of fat particles was observed in PDT group and LDG group, while no infiltration of lipid droplet was found in MDG group and HDG group.Compared with HFD group, the levels of AST, ALT, AKP, TC, TG and LDL-C were significantly decreased after 4-week treatment in PDT group, LDG group, MDG group and HDG group (P<0.05), these indexes were further reduced after 8-week treatment. After 4-week treatment, HDL-C was significantly increased in the 4 treatment groups and almost restored to the level of CON group after 8-week treatment.The levels of CoASH1, CACTI and ACOX1 in the liver tissue of the 4 treatment groups were significantly increased after 4-week treatment (P<0.05) and much improved after 8-week treatment, and those in MDG group and HDG group were better than those in PDT group (P<0.05).CONCLUSION:Ginsenoside Rg1 regulatesβ-oxidation-related enzymes to improve the fat metabolism, thus playing a therapeutic role in liver injury in the rats with NAFLD.

Functional Studies of Acyl-CoA Synthetase 4 in the Rat Liver

Acyl-CoA synthetase 4 (ACS4) is an arachidonate-preferring enzyme abundant in steroidogenic tissues. We examined ACS4 in rat liver, which contains a variety of pathways that use acyl-CoAs, in order to determine subcellular locations. We demonstrate that ACS4 protein was present most abundantly in the mitochondria and to a much lesser extent in the peroxisomes and microsomes. To determined the dietary effects on the level of ACS4 mRNA, northern blotting was carried out using total RNA from the livers of adult male rats fed various diets. Fasting, high fat diet, and fat-free high sucrose diet increased the hepatic level of ACS4 mRNA approximately 2-fold. Furthermore, the levels of ACS4 mRNA were induced by DEHP[Di- (2-ethylhexyl) phthalate]. These data suggest that ACS4 expression in the liver is regulated with a variety of pathways, including beta-oxidation, hormone, and insulin.

Effects of organophosphorus compounds, prothiofos, cyanofenphos and chlorpyrifos on lipid metabolism in rats / 日本農村医学会雑誌

In order to observe the effects of organophosphorus compounds on lipid metabolism, 4mg of prothiofos, cyanofenphos or 1mg of chlorpyrifos were administered per os to different groups of rats, and the results were as follows;<BR>1) Serum cholinesterase activity was significantly suppressed in the experimental group administered these pesticides compared with the control group, administered salad oil only.<BR>2) The lipase activity in the liver was suppressed by administration of prothiofos and that in the kidney was also suppressed by cyanofenphos. There was a close positive correlation between the cholinesterase and lipase activity in epididymal adipose tissues of rats administered prothiofos or cyanofenphos. Furthermore, the positive correlation between the cholinesterase and lipase activity in the kidney was close on day 2 after administration.<BR>3) The acyl CoA synthetase activity in the liver of rats administered cyanofenphos was signifcantly lower than that of the control group, and there was close positive correlation between the cholinesterase and acyl CoA synthetase activity in the rats administered prothiofos.<BR>4) The serum concentration of beta-lipoprotein decreased in the group administered cyanofenphos or chlorpyrifos.<BR>5) The suppression of the lipase and acyl CoA synthetase activity was independent of the serum concentration of immunoreactive insulin.