Effect of dietary methionine on plasma and liver cholesterol concentrations in rats and expression of hepatic genes involved in cholesterol metabolism

Abstract

Methionine has been shown to increase plasma cholesterol in animals. In the present study, mechanisms were investigated by which methionine could alter cholesterol metabolism. In the first experiment, forty growing rats were fed four casein-based diets differing in methionine content (2·6, 3·5, 4·5 or 6·0 g/kg) for 14 d. In the second experiment, isolated rat hepatocytes were incubated in media supplemented with 50, 100 or 200 mmol/l methionine. Dietary methionine tended to increase plasma homocysteine concentrations in the rats (P¼0·058). A weak positive correlation between circulating homocysteine and plasma cholesterol was observed (R 2 0·27, P,0·01). Rats fed 3·5 g/kg or more of methionine had higher concentrations of cholesterol in their plasma, in lipoprotein fractions of density (r; kg/l) 1·006 , r , 1·063 and r . 1·063, and in liver than rats fed 2·6 g/kg methionine. Rats fed 6 g/kg methionine had a higher hepatic expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase and cholesterol-7a-hydroxylase than rats fed less methionine. The phosphatidylcholine:phosphatidylethanolamine ratio in rat liver increased with rising dietary methionine concentration; the relative mRNA concentrations of phosphatidylethanolamine N-methyltransferase and cystathionine b-synthase remained unaffected. Hepatocytes incubated in media supplemented with 100 or 200 mmol/l methionine had a higher cholesterol synthesis than hepatocytes incubated in a medium supplemented with 50 mmol/l methionine; the LDL uptake in hepatocytes was independent of the methionine concentration of the medium. In conclusion, the present study suggests that dietary methionine induces hypercholesterolaemia at least in part via an enhanced hepatic cholesterol synthesis. Previous studies on the effects of dietary proteins on plasma cholesterol have shown that casein raises serum and LDL-cholesterol concentration in animals and man, whereas plant proteins such as soya protein do not (Ikeda et al.

Addition of Methionine to Rice Protein Affects Hepatic Cholesterol Output Inducing Hypocholesterolemia in Rats Fed Cholesterol-Free Diets

“…This finding, consistent with previous studies, 27 suggests that a compensatory increase in hepatic cholesterol synthesis resulting from increased 3-hydroxy-3-methylglutarylcoenzyme A reductase expression might result from Met supplementation in RP.…”

Beneficial Effects of Donepezil on Vascular Endothelial Dysfunction-Associated Dementia Induced by L-Methionine in Rats

“…[32][33][34] Methionine-rich diet in rats has been demonstrated to enhance cholesterol concentration in plasma and liver. 35) Several studies have revealed high serum cholesterol level as another important risk factor of AD. 36) Therefore chronic Lmethionine-induced memory dysfunction in the present study may be attributed to its multiple effects i.e.…”

The Antisteatotic and Hypolipidemic Effect of Insect Meal in Obese Zucker Rats is Accompanied by Profound Changes in Hepatic Phospholipid and 1‐Carbon Metabolism

“…An obvious characteristic of insect meal compared to other animal proteins such as casein is the markedly lower content of the essential sulphur‐containing amino acid methionine. Interestingly, a high intake of methionine is associated with an increased cardiovascular disease risk in men and supplementation of methionine was found to exert a marked hyperlipidemic action . In contrast, methionine restriction was found to induce a coordinated series of transcriptional and biochemical changes including a marked inhibition of hepatic lipid synthesis and consequently antisteatotic and hypolipidemic effects .…”