scholarly journals Inhibition of sterol but not fatty acid synthesis by valproate in developing rat brain in vivo

1990 ◽  
Vol 272 (1) ◽  
pp. 251-253 ◽  
Author(s):  
J P Bolaños ◽  
J M Medina ◽  
D H Williamson

The effect of administration of valproate on lipogenesis in the developing rat brain in vivo was studied. Valproate inhibited by 21-38% the rate of 3H2O incorporation into brain sterols, without significantly affecting fatty acid synthesis. Similarly, R-[2-14C]mevalonate incorporation into sterols was inhibited by 33-54%; the low rate of fatty acid synthesis under these conditions was not affected by valproate. Plasma ketone bodies decreased after treatment with valproate. Valproate inhibited (about 50%) both sterol and fatty acid synthesis in livers of weanling rats. It is concluded that valproate can specifically inhibit sterol synthesis in the brain during development, in part at a stage after mevalonate formation, and also by decreased exogenous precursor supply.

1961 ◽  
Vol 39 (4) ◽  
pp. 739-746 ◽  
Author(s):  
Frank Sauer

Non-diabetic ketosis was produced experimentally in fasted pregnant guinea pigs. Total CO2output of ketotic animals was less than that of appropriate controls but there was no impairment in the conversion of acetate-1-C14to C14O2. Sterol synthesis increased in ketotic animals while fatty acid synthesis, particularly in carcass, showed the expected decrease. Ketosis was accompanied by an increase in plasma total fatty acids and in the fatty acid concentration of liver. The experimental findings support the hypothesis that ketosis is a manifestation of increased ketogenesis rather than impaired utilization of ketone bodies.


1972 ◽  
Vol 102 (5) ◽  
pp. 617-623 ◽  
Author(s):  
D. L. Ingle ◽  
D. E. Bauman ◽  
U. S. Garrigus

2000 ◽  
Vol 22 (1) ◽  
pp. 39-50 ◽  
Author(s):  
Xiaoming Bao ◽  
Manfred Focke ◽  
Mike Pollard ◽  
John Ohlrogge

2000 ◽  
Vol 80 (1) ◽  
pp. 59-67 ◽  
Author(s):  
J. A. Moibi ◽  
R. J. Christopherson ◽  
E. K. Okine

Twenty-four wether lambs were randomly allocated to six treatments to investigate the effect of temperature and dietary lipid supplements on fatty acid synthesis and metabolic activity in sheep. The treatments consisted of four groups exposed to either cold (0 °C) or warm temperature (+23 °C) and given ad libitum access to either a control barley-based diet or with lipid supplementation. Two other groups were placed on the dietary regimen at 0 °C, but pair-fed to intake of animals in the +23 °C environment. At 5 wk, fatty acid synthesis was measured by [1-14C]acetate incorporation into tissue lipids. Cold exposure and dietary lipid supplementation had no effect (P > 0.05) on in vivo fatty acid synthesis rates in either longissimus dorsi or the liver. In both subcutaneous and mesenteric adipose tissue depots, the rate of acetate incorporation into tissue lipid was not significantly affected by cold exposure. In the perirenal fat depot, cold exposure increased (P < 0.05) the rate of fatty acid synthesis, while lipid supplementation decreased (P < 0.05) the rate in all tissue adipose depots. In vitro, mesenteric and perirenal adipose tissues from cold pair-fed animals had higher (P < 0.05) rates of fatty acid synthesis compared to tissues from animals in the warm environment. However, there was no effect of dietary lipid supplementation in these two fat depots. Metabolic heat production, and energy and nitrogen excretion by animals were increased (P < 0.05) by cold exposure while lipid supplementation had the opposite effect (P < 0.05). The relationship between average daily gain and feed intake was linear at both warm and cold environments, but with higher (P < 0.05) average daily gain at all levels of intake in the cold compared to the warm environment. Results indicate that both environment and diet regulate metabolic activity in sheep. However, there were differences in lipogenic response by tissues to the treatments. Key words: Environmental temperature, dietary lipid, fatty acid synthesis, metabolic rate, sheep


1984 ◽  
Vol 52 (1) ◽  
pp. 131-137 ◽  
Author(s):  
G. R. Herzberg ◽  
Minda Rogerson

1. The effect of feeding casein, lactalbumin, soya-bean protein, gluten or gelatin on hepatic lipogenesis and the levels of hepatic fatty acid synthetase (FAS), glucose-6-phosphate dehydrogenase (EC 1. 1. 1.49; G6PD), malic enzyme (EC 1. 1. 1.40; ME) ATP-citrate lyase (EC 4. 1. 3. 8; CL), acetyl CoA carboxylase (EC 6.4.1.2; ACCx) and glucokinase (EC 2. 7. 1. 2; GK) was examined in young growing rats.2. The total activities of ACCx, FAS, CL, GK, G6PD, GK, ME and fatty acid synthesis in vivo were positively correlated with protein quality.3. The specific activities of ACCx, FAS, CL, G6PD and fatty acid synthesis in vivo were positively correlated with protein quality.4. The specific activities of GK and ME were unrelated to protein quality.5. The results demonstrate a dissociation between ME and hepatic lipogenesis and suggest a role for the NADPH generated by ME which is not related to the needs of fatty acid synthesis.


2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi199-vi199
Author(s):  
Gino Ferraro ◽  
Ahmed Ali ◽  
Alba Luengo ◽  
Amy Deik ◽  
Keene Abbott ◽  
...  

Abstract Brain metastases are refractory to therapies that control systemic disease in patients with human epidermal growth factor receptor 2-positive breast cancer and the brain microenvironment contributes to this therapy resistance. Nutrient availability can vary across tissues, therefore metabolic adaptations required for brain metastatic breast cancer growth may introduce liabilities that can be exploited for therapy. Here we assessed how metabolism differs between breast tumors in brain versus extracranial sites and found that fatty acid synthesis is elevated in breast tumors growing in the brain. We determine that this phenotype is an adaptation to decreased lipid availability in the brain relative to other tissues, resulting in site-specific dependency on fatty acid synthesis for breast tumors growing at this site. Genetic or pharmacological inhibition of fatty acid synthase reduces human epidermal growth factor receptor 2-positive breast tumor growth in the brain, demonstrating that differences in nutrient availability across metastatic sites can result in targetable metabolic dependencies.


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