Fatty Acid Synthesis by Rat Liver after Chronic Ethanol Feeding with a Low-Fat Diet

1994 ◽  
Vol 87 (4) ◽  
pp. 441-446 ◽  
Author(s):  
K. J. Simpson ◽  
S. Venkatesan ◽  
T. J. Peters

1. Chronic alcohol feeding with a low-fat diet (4.4% total calories) produced a two- to three-fold increase in hepatic triacylglycerol and esterified cholesterol compared with pair-fed low-fat diet controls. Plasma lipids were similar in both groups. 2. Hepatic fatty acid synthesis rates measured in vivo with 3H2O were significantly lower in the alcohol-fed animals than in controls. Activities of hepatic fatty acid synthase (EC 2.3.1.85) and acetyl-CoA carboxylase (EC 6.4.1.2) were reduced in the alcohol-fed rats. 3. These results indicate that enhanced hepatic fatty acid synthesis does not occur in rats fed alcohol and a low-fat diet for 4 weeks, and is thus not implicated in the pathogenesis of alcohol-induced fatty liver.

1981 ◽  
Vol 45 (3) ◽  
pp. 529-538 ◽  
Author(s):  
G. R. Herzberg ◽  
Minda Rogerson

1. The effect of varying dietary levels of casein (40–140 g/kg) 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), citrate cleavage enzyme (EC 4.1.3.8;CCE), acetyl CoA carboxylase (EC 6.4.1.2; AcCx), glucokinase (EC 2.7.1.2; GK), and pyruvate dehydrogenase (PDH) was examined in young, growing rats.2. The activities of AcCx, FAS, G6PD and in vivo fatty acid synthesis were generally found to increase with increased dietary protein.3. The levels of GK and PDH were not related to dietary protein.4. ME decreased with increasing dietary protein.5. The results demonstrate a dissociation between hepatic fatty acid synthesis and ME and suggest that when rats consume low-protein diets the NADPH needed for fatty acid synthesis is generated primarily by ME but that as the level of dietary protein is increased the contribution of ME is reduced while that of the phosphogluconate pathway becomes more important.


1980 ◽  
Vol 43 (2) ◽  
pp. 349-356 ◽  
Author(s):  
R. Fears ◽  
Elspeth A. Murrellt

1. Hepatic fatty acid synthesis, measured in vivo using 8H2O, was increased by a single dose of L-tryptophan (50 mg/kg body-weight) to both fed and fasted rats and by a supplement of tryptophan to the diet (2.5 g/kg diet for 7 d) when the rats were killed midway through the feeding period.2. Additional dietary tryptophan was hypotriglyceridaemic in normal rats but exacerbated the hyper- triglyceridaemia in rats when lipoprotein clearance was impaired 24 h after an injection of Triton WR 1339 (Chromatography Services Co., Birkenhead, Cheshire).3. The effects of tryptophan on hepatic fatty acid synthesis and the concentration of serum triglyceride were not directly related to the action of the amino acid on gluconeogenesis. A lack of correlation between inhibition of gluconeogenesis and enhancement of lipogenesis was confirmed using mercaptopicolinic acid, a specific inhibitor of phosphoenolpyruvate carboxykinase (EC 4.1.1.32).4. DL-Tryptophan itself did not provide a significant contribution of substrate to the total rate of lipogenesis. Other possible explanations for the activity of tryptophan noted in the present experiments are discussed.5. In conclusion, moderate intakes of tryptophan affect fatty acid and triglyceride metabolism under physiological conditions and it is proposed that the amino acid may be involved in the control of lipid metabolism in a variety of metabolic states.


1991 ◽  
Vol 58 (2) ◽  
pp. 123-127 ◽  
Author(s):  
Emmanuel A. Asante ◽  
William G. Hill ◽  
Grahame Bulfield

SummaryThe flux through the de novo fatty acid synthesis pathway was estimated in lines of mice which differed substantially in fat content following 26 generations of selection at 10 weeks of age. Previous estimates of lipogenic enzyme activities had indicated an increase in the capacity for lipogenesis in the Fat compared to the Lean line. Therefore the in vivo flux in lipogenesis was measured in both liver and gonadal fat pad (GFP) tissues of males at 5 and 10 weeks of age, using the rat of incorporation of 3H from 3H2O and 14C from acetate and citra te into total lipids. AT both ages and in both tissues the Fat line had a higher flux, about 20% increase in the liver and up to three-fold increase (range 1·2- to 3·4-fold) in the GFP. We conclude that direct selection for fatness in mice has resulted in metabolic changes in the ratio of de novo fatty acid synthesis, and that the changes are largely detectable before 10 weeks, the age of selection.


1988 ◽  
Vol 29 (10) ◽  
pp. 1327-1335
Author(s):  
C Grunfeld ◽  
J A Verdier ◽  
R Neese ◽  
A H Moser ◽  
K R Feingold

1987 ◽  
Vol 73 (2) ◽  
pp. 159-163 ◽  
Author(s):  
S. Venkatesan ◽  
R. J. Ward ◽  
T. J. Peters

1. Liver slices from chronically alcohol-fed rats incubated with 3H2O showed less than half the fatty acid synthesis rates of pair-fed controls. Addition of 50 mmol/l ethanol or of 10 mmol/l lactate and 1 mmol/l pyruvate to the incubation medium did not alter the fatty acid synthesis rates in either groups. Hepatic fatty acid synthesis rates measured in vivo with 3H2O were also significantly reduced in alcohol-fed rats. 2. Time-course experiments showed that after 1 week on the ethanol diet hepatic fatty acid synthesis rates in vitro were similar to control rats, although the liver triacylglycerol content was significantly increased. From the second week of feeding, fatty acid synthesis rates were significantly lower in alcohol-fed rats and the liver triacylglycerol content progressively increased compared with controls. 3. Fatty acid synthase activity in liver cytosolic fractions were similar to controls in the alcohol-fed group after 1 week of feeding but were significantly lower in alcohol-fed rats from the second week onwards. 4. These results indicate that hepatic triacylglycerol accumulation after alcohol feeding is not due to increased fatty acid synthesis. The reduced fatty acid synthesis observed is a consequence of triacylglycerol accumulation.


2020 ◽  
Author(s):  
Ganghua Tang ◽  
Shaoyu Liu ◽  
Ping Hu ◽  
Hui Ma ◽  
Xianhong Xiang ◽  
...  

Abstract BackgroundThe aim of this study was to evaluate the potential value of 2-[18F]fluoropropionic acid ([18F]FPA) for PET imaging of prostate cancer (PCa) and to confirm the correlation between [18F]FPA accumulation and fatty acid synthase (FASN) levels in PCa models. The results of the first [18F]FPA PET study of a PCa patient are reported.MethodsA PET imaging comparison of [18F]FDG and [18F]FPA was performed in LNCaP, PC-3 and DU145 tumors. Additionally, in vivo blocking experiments in those models were conducted with orlistat. Western blotting staining of FASN were performed in the those xenograft tumors.ResultsThe uptake of [18F]FPA in the LNCaP and PC-3 tumors was higher than that of [18F]FDG (P<0.05 and P<0.05), while [18F]FDG was significantly superior to [18F]FPA in detecting DU145 tumors (P<0.05). Grayscale scanning showed that FASN expression in the LNCaP and PC-3 tumors was 33.3% and 10.3% higher than that in the DU145 tumors, respectively. The accumulation (% ID/g) of [18F]FPA in the LNCaP , PC-3 and DU145 tumors decreased by 27.6, 40.5 and 11.7%, respectively, after treatment with orlistat. The [18F]FPA showed higher tumor/background ratios than [18F]FDG in the first PCa patient (P<0.05).ConclusionsThe [18F]FPA uptake in PCa models was positively correlated with FASN expression and could be reduced after administration of a single FASN inhibitor. In addition, the [18F]FPA is a potential broad-spectrum PET imaging agent, and the imaging effect of [18F]FPA may be superior to [18F]FDG in human PCa.


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