Metabolism of short chain fatty acid in rat liver in biliary obstruction.

Koyama, Kenji; Kashimura, S.; Yamauchi, Hidemi; Takagi, Yasushi; Owada, Yasuo; Sato, Toshio

doi:10.1620/tjem.117.335

Cited by 14 publications

(3 citation statements)

References 5 publications

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“…Although a change in plasma ketone body utilization can not be excluded, the data support the hypothesis that hepatic ketogenesis is impaired in BDL rats. Impaired ketogenesis from butyrate has been reported with liver slices or perfused liver from BDL dogs (33) or rats (34). Similar changes in hepatic lipid metabolism have been reported in rats with acute liver disease induced by CC1, (35).…”

Section: Discussionsupporting

confidence: 70%

Fuel homeostasis and carnitine metabolism in rats with secondary biliary cirrhosis

Krähenbühl

Brass

1991

Hepatology

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Energy metabolism is abnormal in patients and experimental animals with liver cirrhosis. To help better understand the abnormalities, fuel homeostasis and carnitine metabolism were studied in fed and 24-hr-starved rats with secondary biliary cirrhosis induced by bile duct ligation for 4 wk. Plasma ketone body concentrations were decreased by 67% in starved, bile duct-ligated rats compared with control rats. In contrast, plasma nonesterified fatty acid concentrations were not different between bile duct-ligated and control rats in the fed or the fasted state. Plasma triglyceride concentrations showed the expected decrease with starvation in control rats, but were increased with starvation in bile duct-ligated rats. Urinary excretion of dicarboxylic acids was increased in both fed and fasted bile duct ligated-rats compared with the respective control groups. Compared with control rats, hepatic total carnitine content (per gram of liver) was increased by 24% in fed and by 36% in fasted, bile duct-ligated rats. Fed, bile duct-ligated rats had an increased short-chain acylcarnitine-to-carnitine ratio in liver, plasma and urine compared with control rats. Analysis of the hepatic coenzyme A pool showed decreased coenzyme A content in fed and fasted bile duct-ligated rats compared with control rats. Hepatic long-chain acylcarnitine and long-chain acyl-coenzyme A content increased with starvation both in control and bile duct-ligated rats. The rise in plasma nonesterified fatty acid concentration and hepatic long-chain acylcarnitine and long-chain acylcoenzyme A contents with starvation in bile duct-ligated rats are consistent with unaltered hepatic availability of fatty acids.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionsupporting

confidence: 70%

Fuel homeostasis and carnitine metabolism in rats with secondary biliary cirrhosis

Krähenbühl

Brass

1991

Hepatology

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“…Early studies had shown that the production of ketone bodies by perfused livers from rats with long-term bile duct ligation is reduced (7). In agreement with these observations, we later found that rats with long-term bile duct ligation, when starved for 24 h, had decreased plasma ketone body concentrations (3) and that the production of ketone bodies by hepatocytes isolated from such rats was lower than for control rats (2).…”

Section: Impaired Hepatic Fatty Acid Oxidation In Rats With Short-term Cholestasis: Characterization and Mechanismsupporting

confidence: 89%

Impaired hepatic fatty acid oxidation in rats with short-term cholestasis: characterization and mechanism

Lang

Schäfer

Serra

et al. 2001

Journal of Lipid Research

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Rats with long-term cholestasis have reduced ketosis during starvation. Because it is unclear whether this is also the case in short-term cholestasis, we investigated hepatic fatty acid metabolism in rats with bile duct ligation for 5 days (BDL5, n ‫؍‬ 11) or 10 days (BDL10, n ‫؍‬ 11) and compared the findings with those made with pair-fed control rats (CON5 and CON10, n ‫؍‬ 11). The plasma ␤ -hydroxybutyrate concentration was reduced in BDL rats (0.54 ؎ 0.10 vs. 0.83 ؎ 0.30 mM at 5 days and 0.59 ؎ 0.24 vs. 0.88 ؎ 0.09 mM at 10 days in BDL and control rats, respectively). In isolated liver mitochondria, state 3 oxidation rates for various substrates were not different between BDL and control rats. Production of ketone bodies from [ 14 C]palmitate was reduced by 40% in mitochondria from BDL rats at both time points, whereas production of 14 CO 2 was maintained. These findings indicated intact function of the respiratory chain, Krebs cycle, and ␤ -oxidation and suggested impaired ketogenesis (HMG-CoA pathway). Accordingly, the formation of acetoacetate from acetyl-CoA by disrupted mitochondria was reduced in BDL rats at 5 days (2.1 ؎ 1.0 vs. 4.8 ؎ 1.9 nmol/min per mg protein) and at 10 days (1.7 ؎ 1.0 vs. 6.2 ؎ 1.9 nmol/min per mg protein). The principal defect could be localized at the rate-limiting enzyme of the HMG-CoA pathway, HMG-CoA synthase, which revealed decreased activity, and reduced hepatic mRNA and protein levels. We conclude that short-term cholestasis in rats leads to impaired hepatic fatty acid metabolism due to impaired ketogenesis. Ketogenesis is impaired because of decreased mRNA levels of HMG-CoA synthase, leading to reduced hepatic protein levels and to decreased activity of this key enzyme of ketogenesis.

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“…In this animal model, decreased metabolism of fatty acids ( 12,13) and decreased mitochondrial oxidative metabolism of succinate and P-hydroxybutyrate have been described ( 141, findings consistent with decreased activity of the mitochondrial electron transport chain. The enzyme complexes of the mitochondrial electron transport chain are located in the inner mitochondrial membrane (15), and the lipid composition of this membrane is critical for normal function of the electron transport chain (15,16).…”

mentioning

confidence: 54%

Toxicity of bile acids on the electron transport chain of isolated rat liver mitochondria

et al. 1994

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The toxicity of hydrophilic (cholate) and lipophilic (deoxycholate, chenodeoxycholate, and lithocholate) bile acids on the function of the electron transport chain was investigated in intact and disrupted rat liver mitochondria. In intact mitochondria, lipophilic bile acids used at a concentration of 100 mumol/L (0.1 mumol/mg protein) inhibited state 3 and state 3u (dinitrophenol-uncoupled) oxidation rates for L-glutamate, succinate, duroquinol or ascorbate/N,N,N',N'-tetramethyl-p-phenylenediamine as substrates. In contrast, state 4 oxidation rates and ADP/oxygen ratios were not significantly affected. At a bile acid concentration of 10 mumol/L (0.01 mumol/mg protein), the state 3 oxidation rate for L-glutamate was decreased in the presence of deoxycholate, chenodeoxycholate or lithocholate, whereas only lithocholate inhibited state 3 oxidation for succinate or duroquinol. In broken mitochondria, inhibition of oxidative metabolism was found for NADH or duroquinol as substrate in the presence of 100 mumol/L lithocholate (0.2 mumol/mg protein) and for duroquinol in the presence of 100 mumol/L chenodeoxycholate. Direct assessment of the activities of the enzyme complexes of the electron transport chain revealed decreased activities of complex I and complex III in the presence of 100 mumol/L deoxycholate or chenodeoxycholate or 10 mumol/L lithocholate. Inhibition of complex IV required higher bile acid concentrations (300 mumol/L for chenodeoxycholate or 30 mumol/L for lithocholate), and complex II was not affected. Both chenodeoxycholate and lithocholate were incorporated into mitochondrial membranes. The phospholipid content of mitochondrial membranes decreased in incubations containing 100 mumol/L (0.1 mumol/mg protein) chenodeoxycholate but was not affected in the presence of 100 mumol/L lithocholate.(ABSTRACT TRUNCATED AT 250 WORDS)

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Metabolism of short chain fatty acid in rat liver in biliary obstruction.

Cited by 14 publications

References 5 publications

Fuel homeostasis and carnitine metabolism in rats with secondary biliary cirrhosis

Fuel homeostasis and carnitine metabolism in rats with secondary biliary cirrhosis

Impaired hepatic fatty acid oxidation in rats with short-term cholestasis: characterization and mechanism

Toxicity of bile acids on the electron transport chain of isolated rat liver mitochondria

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