Sex difference in human mevalonate metabolism.

Feingold, Kenneth R.; Wiley, Millie Hughes; Searle, G. L.; Machida, B K; Siperstein, Marvin D.

doi:10.1172/jci109864

Cited by 25 publications

(8 citation statements)

References 22 publications

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“…The studies of Kelly and Kratz have shown that increased mevalonate shunt activity does occur in SLOS patients, as they excrete significant amounts of 3-methylglutaconic acid (49). Other reports have shown that it is not unusual for the mevalonate shunt pathway to divert as much as 30-45% of mevalonate away from sterol synthesis (50)(51)(52)(53). Being female, sex hormones, fasting, and experimental diabetes increased the shunt activity by 30-35% (50-53).…”

Section: Downloaded Frommentioning

confidence: 99%

Feedback inhibition of the cholesterol biosynthetic pathway in patients with Smith-Lemli-Opitz syndrome as demonstrated by urinary mevalonate excretion

Pappu

Steiner

Connor

et al. 2002

Journal of Lipid Research

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Smith-Lemli-Opitz syndrome (SLOS) is a genetic disorder characterized by low plasma cholesterol and high 7-dehydrocholesterol (7-DHC). Synthesis of cholesterol and 7-DHC and its metabolites is regulated by HMG-CoA reductase, whose activity can be measured by 24-h excretion of its product mevalonate. We devised a simple, non-invasive method for collecting 24-h urine in our subjects. With a background of a very low cholesterol diet, mean mevalonate excretion did not differ between controls and SLOS children, indicating that SLOS subjects have normal HMGCoA reductase activity. In a short term feeding study, the effects of a high cholesterol diet in SLOS subjects include a significant 55% increase in plasma cholesterol levels and 39% decrease in mevalonate excretion and no change in plasma 7-DHC levels. However, in four SLOS subjects, fed a high cholesterol diet for 2-3 years, plasma cholesterol levels continued to increase, urinary mevalonate excretion remained low and total 7-DHC decreased significantly, likely from decreased total sterol synthesis.Thus, in SLOS subjects, HMG-CoA reductase activity was normal and was subject to normal cholesterol induced feedback inhibition. However, total sterol synthesis in SLOS may still be decreased because of increased diversion of mevalonate into the shunt pathway away from sterol synthesis. -

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Section: Downloaded Frommentioning

confidence: 99%

Feedback inhibition of the cholesterol biosynthetic pathway in patients with Smith-Lemli-Opitz syndrome as demonstrated by urinary mevalonate excretion

Pappu

Steiner

Connor

et al. 2002

Journal of Lipid Research

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“…Pang et al (2008) also showed that the extract of I. paraguariensis decreased the blood and liver concentrations of lipids, as well as levels of glucose. Differences between males and females in the effect of I. paraguariensis on cholesterol levels may have been due to the females having double the renal capacity to convert mevalonate into CO 2 , compared to that of males, while the latter have an increased capacity to convert plasma cholesterol (Feingold et al, 1980).…”

Section: Resultsmentioning

confidence: 99%

Effect of erva-mate (Ilex paraguariensis A. St.-Hil., Aquifoliaceae) on serum cholesterol, triacylglycerides and glucose in Wistar rats fed a diet supplemented with fat and sugar

Przygodda¹,

Martins²,

Castaldelli³

et al. 2010

Rev. bras. farmacogn.

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956RESUMO: "Efeito da erva-mate (Ilex paraguariensis A. St.-Hil., Aquifoliaceae) sobre o colesterol, triacilglicerídeos e glucose em ratos Wistar com dieta alimentar suplementada com lipídeos e glicídeos" Ilex paraguariensis A. St.-Hil., Aquifoliaceae, é uma espécie nativa das regiões subtropicais e temperadas da América do Sul, usada em bebidas por infusão como chá, chimarrão e tererê. Para verificar os efeitos fisiológicos que a I. paraguariensis pode causar sobre o metabolismo de lipídeos e glicídeos em ratos Wistar, após a ingestão de chá de erva-mate, analisou-se quatro grupos experimentais: Grupo Lipídeo Controle (receberam água e dieta hiperlipídica); Grupo Lipídeo Ingestão (extrato de I. paraguariensis e dieta hiperlipídica); Grupo Glicídeo Controle (receberam água e dieta hiperglicídica); e Grupo Glicídeo Ingestão (extrato de I. paraguariensis e dieta hiperglicídica). Os animais receberam a dieta por 60 dias, de acordo com o grupo que pertenciam, sendo pesados semanalmente. Após esse período, foram avaliadas as concentrações de colesterol, glicose e triacilglicerídeos sanguíneos, e ainda, peso da gordura visceral. Os dados foram analisados estatísticamente. O nível de significância aceito foi p<0,05. Os resultados mostraram que a ingestão de erva-mate atua sobre o peso corpóreo, gordura visceral e taxas de glucose, colesterol e triacilglicerídeos plasmáticos. Unitermos: Ilex paraguariensis, metabolismo de lipídios, metabolismo de glicídios.ABSTRACT: Ilex paraguariensis A. St.-Hil., Aquifoliaceae, is a species native to the subtropical and temperate regions of South America, used in beverages prepared by infusion such as teas, chimarrão and tererê. To investigate the physiological effects of I. paraguariensis on the metabolism of fats and sugars in Wistar rats, following the ingestion of erva-mate tea, four experimental groups were constructed: Lipid Control Group (receiving water and high-fat diet); Lipid Tea Group (extract of I. paraguariensis and high-fat diet); the Sugar Control Group (water and high-sugar diet); and Sugar Tea Group (extract of I. paraguariensis and high-sugar diet). The animals received their particular diet for 60 days, and were weighed weekly. After this period, the plasma concentrations of cholesterol, glucose and triacylglycerides were determined, together with the weight of visceral fat. The data were subjected to statistical analysis with a significance level of p<0.05. The results show that the ingestion of erva-mate affected body weight, visceral fat and plasma glucose, cholesterol and triacylglyceride levels. Keywords:Ilex paraguariensis, fat metabolism, sugar metabolism.Revista Brasileira de Farmacognosia Brazilian Journal of Pharmacognosy 20(6): 956-961, Dez. 2010 Article

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“…Observations of circutlating mevalonate metalbolism in castratedn male rats and immatture female rats have impliedl that these sex differences are secondary to the effects of sex hormones (15). In humans, premenopausal femailes oxidize 68% more circulatinig mevalonate to CO2 than age-maitche(d imiales (16). Insulini-deficient, streptozotocin-treated rats also deinonstrate a marked reduction in shuint activity and an increase in sterologenesis (17 (12 uimlol in miiales an(I 21 nmol in femailes).…”

Section: Discussionmentioning

confidence: 99%

“…These sex differ-ences in the metabolism of circtulatinig mevalonate are dlue entirely to (liffereinces in renial metabolism (15). Recentlv, a sex differenice in circuilating mevalonate metalbolism has also l)eeni demonstratedi in humtiiianis; premenopautsal women oxidize 68% miiore eirculatinig mevalonate to CO2 thain age-matchedimales (16).…”

Section: Introductionmentioning

confidence: 99%