A new method for assaying rat liver microsomal 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity and its application in a study of the effect of dietary cholesterol on this effect of dietary cholesterol on this enzyme

Schisandrin B (SchB) is one of the most abundant bioactive dibenzocyclooctadiene derivatives found in the fruit of Schisandra chinensis. Here, we investigated the potential therapeutic effects of SchB on non-alcoholic fatty-liver disease (NAFLD). In lipidomic study, ingenuity pathway analysis highlighted palmitate biosynthesis metabolic pathway in the liver samples of SchB-treated high-fat-diet-fed mice. Further experiments showed that the SchB treatment reduced expression and activity of fatty acid synthase, expressions of hepatic mature sterol regulatory element binding protein-1 and tumor necrosis factor-α, and hepatic level of palmitic acid which is known to promote progression of steatosis to steatohepatitis. Furthermore, the treatment also reduced hepatic fibrosis, activated nuclear factor-erythroid-2-related factor-2 which is known to attenuate the progression of NASH-related fibrosis. Interestingly, in fasting mice, a single high-dose SchB induced transient lipolysis and increased the expressions of adipose triglyceride lipase and phospho-hormone sensitive lipase. The treatment also increased plasma cholesterol levels and 3-hydroxy-3-methylglutaryl-CoA reductase activity, reduced the hepatic low-density-lipoprotein receptor expression in these mice. Our data not only suggest SchB is a potential therapeutic agent for NAFLD, but also provided important information for a safe consumption of SchB because SchB overdosed under fasting condition will have adverse effects on lipid metabolism.

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“…The HMG-CoA reductase activity was measured as described 57 . Briefly, liver tissues were homogenized and centrifuged.…”

Section: Methodsmentioning

confidence: 99%

Lipidomic-based investigation into the regulatory effect of Schisandrin B on palmitic acid level in non-alcoholic steatotic livers

Kwan

Niu

Dai

et al. 2015

Sci Rep

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“…Other analytical methods Free CoA was measured essentially as described (Garland et al, 1965;Baqir & Booth, 1977), measuring formation of NADH at 340 nm using a Beckman Model 26 spectrophotometer.…”

Section: Hplc Analysismentioning

confidence: 99%

The metabolism of tetradecylthiopropionic acid, a 4-thia stearic acid, in the rat. In vivo and in vitro studies

Hvattum

Skrede

Bremer

et al. 1992

Biochemical Journal

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The metabolism of [1-14C]tetradecylthiopropionic acid (TTP), a 4-thia stearic acid, and its sulphoxide, [1-14C]texadecylsulphoxypropionic acid (TTP-SO), has been studied in intact rats, in isolated rat hepatocytes, and in rat liver mitochondria. Two pathways of oxidation (beta-oxidation and omega-oxidation) have been demonstrated. TTP is incorporated, in vivo, into tissue triacylglycerol and phospholipids, it is oxidized to CO2, and it is excreted in urine, mainly as carboxypropylsulphoxypropionic acid and a little as carboxymethylsulphoxypropionic acid. TTP-SO is metabolized, in vivo, more rapidly to the same two omega-oxidation products. In hepatocytes TTP is incorporated into triacylglycerol and phospholipids even more rapidly than stearic acid. It is recovered mainly in the 1-position of phosphatidylcholine. Some is oxidized to CO2 and acid-soluble products. TTP-SO is mainly omega-oxidized to the same metabolites as are found in urine. A small fraction is incorporated into phospholipids or oxidized to CO2. In isolated mitochondria [1-14C]TTP is converted into 14CO2, radioactive malonic semialdehyde, and addition products of malonic semialdehyde. In the presence of phenylhydrazine, malonic semialdehyde phenylhydrazone is the dominating product. In soluble extracts of mitochondria [1-14C]malonic semialdehyde is oxidized directly to 14CO2 in the presence of CoA and NAD+, probably by the (methyl)malonic acid semialdehyde dehydrogenase (EC 1.2.1.27).

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“…Separated rat plasma lipoproteins, prepared as in [8] were kindly provided by Dr E. R. Skinner, Department of Biochemistry, Marischal College, University of Aberdeen. Cholesterol and cholesteryl ester were extracted from cell suspensions, isolated by TLC and estimated by procedures used for sterol analysis of microsomal suspensions [9]. this rate was also ~l/8th of that given by cells from rats not treated with 4-APP (table 1A).…”

Section: Methodsmentioning

confidence: 99%

Evidence for an essential role for high‐density lipoprotein in progesterone synthesis by rat corpus luteum

1981

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A new method for assaying rat liver microsomal 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity and its application in a study of the effect of dietary cholesterol on this effect of dietary cholesterol on this enzyme

Cited by 12 publications

References 32 publications

Lipidomic-based investigation into the regulatory effect of Schisandrin B on palmitic acid level in non-alcoholic steatotic livers

Lipidomic-based investigation into the regulatory effect of Schisandrin B on palmitic acid level in non-alcoholic steatotic livers

The metabolism of tetradecylthiopropionic acid, a 4-thia stearic acid, in the rat. In vivo and in vitro studies

Evidence for an essential role for high‐density lipoprotein in progesterone synthesis by rat corpus luteum

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