3-Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase produces mevalonate, an important intermediate in the synthesis of cholesterol and essential nonsterol isoprenoids. The reductase is subject to an exorbitant...3-Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase produces mevalonate, an important intermediate in the synthesis of cholesterol and essential nonsterol isoprenoids. The reductase is subject to an exorbitant amount of feedback control through multiple mechanisms that are mediated by sterol and nonsterol end-products of mevalonate metabolism. Here, I will discuss recent advances that shed light on one mechanism for control of reductase, which involves rapid degradation of the enzyme. Accumulation of certain sterols triggers binding of reductase to endoplasmic reticulum (ER) membrane proteins called Insig-1 and Insig-2. Reductase-Insig binding results in recruitment of a membrane-associated ubiquitin ligase called gp78, which initiates ubiquitination of reductase. This ubiquitination is an obligatory reaction for recognition and degradation of reductase from ER membranes by cytosolic 26S proteasomes. Thus, sterol-accelerated degradation of reductase represents an example of how a general cellular process (ER-associated degradation) is used to control an important metabolic pathway (cholesterol synthesis).展开更多
In order to study the effects of Ampelopsis grossedentata on endogenous cholesterol biosynthesis and the effects of reducing blood lipid in hyperlipidemia rats,extraction of flavonoids from Ampelopsis grossedentata by...In order to study the effects of Ampelopsis grossedentata on endogenous cholesterol biosynthesis and the effects of reducing blood lipid in hyperlipidemia rats,extraction of flavonoids from Ampelopsis grossedentata by using ethanol(TFAG),and the effects of TFAG on intracellular cholesterol synthesis were detected by amphotericin B-cell model;SD hyperlipidemia rat model was established by feeding high fat diet.A formulated medicine called Xuezhikang was used as a positive control,and TFAG of different doses were administered to the stomach for 30 d continuously to measure the indexes of heart,liver tissue homogenate and serum;part of the liver was taken for pathological observation.The results showed that TFAG could significantly inhibit the synthesis of cholesterol in cells.TFAG of different doses could significantly reduce the content of TC and TG in serum of hyperlipidemia rats,and increase the content of HDL;TC and TG in heart and liver were also decreased;besides,it could increase the content of SOD,CAT and GSH in the liver of hyperlipidemia rats,and reduce the content of MDA.The results of pathological section showed that TFAG could improve the damage degree of hepatocytes in hyperlipidemia rats,and the effect of high dose group was similar to that of Xuezhikang group.In general,TFAG has good antioxidant and reducing blood lipid effects,and can effectively inhibit liver steatosis.展开更多
This study was aimed to determine the effects of dried black cumin and tamarind supplementation on egg performance and lipids concentration in egg yolk of layer hens. Sixty laying hens at the age of 18-34 weeks were d...This study was aimed to determine the effects of dried black cumin and tamarind supplementation on egg performance and lipids concentration in egg yolk of layer hens. Sixty laying hens at the age of 18-34 weeks were divided into 4 treatments (control, 1% black cumin, 4% tamarind and 1% black cumin + 4% tamarin in diets) with 4 replications each (15 birds/replication). The experimental treatments were subjected to completely randomized design. Feed and drinking water were provided ad-libitum. 16 h per day for lighting program during experimental period. The results found that feed efficiency ratio, egg production and egg weight were no significant between treatments. However, average daily feed intake was highest in 4% tamarind and 1% black cumin + 4% tamarin in diets. Egg yolk color score, yolk index, white index and shell tickness were no significantly different, However, haugh unit was lowest in control group. Egg yolk lipids concentration was founded that black cumin and tamarind in diet were reduced cholesterol and triacyl-glycerol concentration with statistical significance (P 〈 0.05). So that dried black cumin and tamarind supplementation in diets were no any effect on egg production and egg weight. Furthermore, egg yolk cholesterol and triacyl-glycerol concentration were decreased. Hence, supplementation of dried black cumin and tamarind in diets could benefit to consumer health.展开更多
The relationship between low levels of serum low-density lipoprotein cholesterol(LDL-C)and subsequent cognitive decline remains unclear.The present study aimed to evaluate the longitudinal association between low LDL-...The relationship between low levels of serum low-density lipoprotein cholesterol(LDL-C)and subsequent cognitive decline remains unclear.The present study aimed to evaluate the longitudinal association between low LDL-C levels and cognition decline in the context of the current aggressive guideline-recommended targets(LDL-C levels less than 55 mg/dL for individuals at very high risk of cardiovascular events,and less than 70 mg/dL for high risk individuals).Data from wave 13(2016)to wave 14(2018)of the Health and Retirement Study(HRS)were utilized.LDL-C concentrations measured at wave 13 were categorized into 5 levels,reflecting currently recommended values for lipid lowering treatment.Of 7129 included participants(mean age:69.0±9.9 years,60.3%female),we found that compared to participants with LDL-C levels of 70.0-99.9 mg/dL,those with LDL-C levels of<55 mg/dL had significantly slower 2-year decline rates in global cognitive function(0.244 point/year;95%confidence interval(CI):0.065-0.422;P=0.008),working memory(0.068 point/year;95%CI:0.004-0.133;P=0.038),and borderline significantly in episodic memory(0.155 point/year;95%CI:-0.004-0.315;P=0.057).Similarly,significantly slower decline rates were observed in those with LDL-C levels of 55.0-69.9 mg/dL.The present study demonstrated that compared with LDL-C levels 70.0-99.9 mg/dL,low LDL-C levels(<70 mg/dL,especially<55 mg/dL)were associated with significantly slower cognitive decline in population-based setting.Future randomized controlled trials are warranted to ascertain the safety and benefit of current aggressive guideline-recommended targets on cognitive function.展开更多
文摘3-Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase produces mevalonate, an important intermediate in the synthesis of cholesterol and essential nonsterol isoprenoids. The reductase is subject to an exorbitant amount of feedback control through multiple mechanisms that are mediated by sterol and nonsterol end-products of mevalonate metabolism. Here, I will discuss recent advances that shed light on one mechanism for control of reductase, which involves rapid degradation of the enzyme. Accumulation of certain sterols triggers binding of reductase to endoplasmic reticulum (ER) membrane proteins called Insig-1 and Insig-2. Reductase-Insig binding results in recruitment of a membrane-associated ubiquitin ligase called gp78, which initiates ubiquitination of reductase. This ubiquitination is an obligatory reaction for recognition and degradation of reductase from ER membranes by cytosolic 26S proteasomes. Thus, sterol-accelerated degradation of reductase represents an example of how a general cellular process (ER-associated degradation) is used to control an important metabolic pathway (cholesterol synthesis).
文摘In order to study the effects of Ampelopsis grossedentata on endogenous cholesterol biosynthesis and the effects of reducing blood lipid in hyperlipidemia rats,extraction of flavonoids from Ampelopsis grossedentata by using ethanol(TFAG),and the effects of TFAG on intracellular cholesterol synthesis were detected by amphotericin B-cell model;SD hyperlipidemia rat model was established by feeding high fat diet.A formulated medicine called Xuezhikang was used as a positive control,and TFAG of different doses were administered to the stomach for 30 d continuously to measure the indexes of heart,liver tissue homogenate and serum;part of the liver was taken for pathological observation.The results showed that TFAG could significantly inhibit the synthesis of cholesterol in cells.TFAG of different doses could significantly reduce the content of TC and TG in serum of hyperlipidemia rats,and increase the content of HDL;TC and TG in heart and liver were also decreased;besides,it could increase the content of SOD,CAT and GSH in the liver of hyperlipidemia rats,and reduce the content of MDA.The results of pathological section showed that TFAG could improve the damage degree of hepatocytes in hyperlipidemia rats,and the effect of high dose group was similar to that of Xuezhikang group.In general,TFAG has good antioxidant and reducing blood lipid effects,and can effectively inhibit liver steatosis.
文摘This study was aimed to determine the effects of dried black cumin and tamarind supplementation on egg performance and lipids concentration in egg yolk of layer hens. Sixty laying hens at the age of 18-34 weeks were divided into 4 treatments (control, 1% black cumin, 4% tamarind and 1% black cumin + 4% tamarin in diets) with 4 replications each (15 birds/replication). The experimental treatments were subjected to completely randomized design. Feed and drinking water were provided ad-libitum. 16 h per day for lighting program during experimental period. The results found that feed efficiency ratio, egg production and egg weight were no significant between treatments. However, average daily feed intake was highest in 4% tamarind and 1% black cumin + 4% tamarin in diets. Egg yolk color score, yolk index, white index and shell tickness were no significantly different, However, haugh unit was lowest in control group. Egg yolk lipids concentration was founded that black cumin and tamarind in diet were reduced cholesterol and triacyl-glycerol concentration with statistical significance (P 〈 0.05). So that dried black cumin and tamarind supplementation in diets were no any effect on egg production and egg weight. Furthermore, egg yolk cholesterol and triacyl-glycerol concentration were decreased. Hence, supplementation of dried black cumin and tamarind in diets could benefit to consumer health.
基金supported by the National Natural Science Foundation of China (81974490)the 2019 Irma and Paul MilsteinProgram for Senior Health Research Project Award。
文摘The relationship between low levels of serum low-density lipoprotein cholesterol(LDL-C)and subsequent cognitive decline remains unclear.The present study aimed to evaluate the longitudinal association between low LDL-C levels and cognition decline in the context of the current aggressive guideline-recommended targets(LDL-C levels less than 55 mg/dL for individuals at very high risk of cardiovascular events,and less than 70 mg/dL for high risk individuals).Data from wave 13(2016)to wave 14(2018)of the Health and Retirement Study(HRS)were utilized.LDL-C concentrations measured at wave 13 were categorized into 5 levels,reflecting currently recommended values for lipid lowering treatment.Of 7129 included participants(mean age:69.0±9.9 years,60.3%female),we found that compared to participants with LDL-C levels of 70.0-99.9 mg/dL,those with LDL-C levels of<55 mg/dL had significantly slower 2-year decline rates in global cognitive function(0.244 point/year;95%confidence interval(CI):0.065-0.422;P=0.008),working memory(0.068 point/year;95%CI:0.004-0.133;P=0.038),and borderline significantly in episodic memory(0.155 point/year;95%CI:-0.004-0.315;P=0.057).Similarly,significantly slower decline rates were observed in those with LDL-C levels of 55.0-69.9 mg/dL.The present study demonstrated that compared with LDL-C levels 70.0-99.9 mg/dL,low LDL-C levels(<70 mg/dL,especially<55 mg/dL)were associated with significantly slower cognitive decline in population-based setting.Future randomized controlled trials are warranted to ascertain the safety and benefit of current aggressive guideline-recommended targets on cognitive function.