Stimulation by acetate of gluconeogenesis in hepatocyte suspensions

Whitton, Patricia D.; Rodrigues, L. M.; Hems, Douglas A.

doi:10.1016/0014-5793(79)80157-x

Cited by 11 publications

(3 citation statements)

References 19 publications

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“…The latter suggestion is supported by the observation that alanine increases gluconeogenesis in perfused livers from starved rats (Williamson et al, 1969), although the effect is abolished by fatty acids. Acetate also enhances glucose synthesis in hepatocytes from starved rats (Whitton et al, 1979). It has been reported that diets high in ethanol increase the activities of two gluconeogenic enzymes in liver and kidney in the rat (Jauhonen et al, 1978) and decrease gluconeogenic amino acids in plasma in sheep (G. B.…”

Section: Metabolic Effects Of Ethaniolmentioning

confidence: 97%

Acute effects of ethanol on the perfused rat liver. Studies on lipid and carbohydrate metabolism, substrate cycling and perfusate amino acids

Topping

Clark

Storer

et al. 1979

Biochemical Journal

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1. Livers from fed rats were perfused in situ with whole rat blood containing glucose labelled uniformly with (14)C and specifically with (3)H at positions 2, 3 or 6. 2. When ethanol was infused at a concentration of 24mumol/ml of blood the rate of utilization was 2.8mumol/min per g of liver. 3. Ethanol infusion raised perfusate glucose concentrations and caused a 2.5-fold increase in hepatic glucose output. 4. Final blood lactate concentrations were decreased in ethanol-infused livers, but the mean uptake of lactate from erythrocyte glycolysis was unaffected. 5. Production of ketone bodies (3-hydroxybutyrate+3-oxobutyrate) and the ratio [3-hydroxybutyrate]/[3-oxobutyrate] were raised by ethanol. 6. Formation of (3)H(2)O from specifically (3)H-labelled glucoses increased in the order [6-(3)H]<[3-(3)H]<[2-(3)H]. Production of (3)H(2)O from [2-(3)H]glucose was significantly greater than that from [3-(3)H]glucose in both control and ethanol-infused livers. Ethanol significantly decreased (3)H(2)O formation from all [(3)H]glucoses. 7. Liver glycogen content was unaffected by ethanol infusion. 8. Production of very-low-density lipoprotein triacylglycerols was inhibited by ethanol and there was a small increase in liver triacylglycerols. Very-low-density-lipoprotein secretion was negatively correlated with the ratio [3-hydroxybutyrate]/[3-oxobutyrate]. Perfusate fatty acid concentrations and molar composition were unaffected by perfusion with ethanol. 9. Ethanol decreased the incorporation of [U-(14)C]glucose into fatty acids and cholesterol. 10. The concentration of total plasma amino acids was unchanged by ethanol, but the concentrations of alanine and glycine were decreased and ([glutamate]+[glutamine]) was raised. 11. It is proposed that the observed effects of ethanol on carbohydrate metabolism are due to an increased conversion of lactate into glucose, possibly by inhibition of pyruvate dehydrogenase. The increase in gluconeogenesis is accompanied by diminished substrate cycling at glucose-glucose 6-phosphate and at fructose 6-phosphate-fructose 1,6-bisphosphate.

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Section: Metabolic Effects Of Ethaniolmentioning

confidence: 97%

Acute effects of ethanol on the perfused rat liver. Studies on lipid and carbohydrate metabolism, substrate cycling and perfusate amino acids

Topping

Clark

Storer

et al. 1979

Biochemical Journal

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“…There is still no theory on the mechanism of VFA absorption which has really gained wide acceptance, particularly in relation to the absorption of cations. In addition, the metabolic fate of the absorbed VFA has seldom been studied, even though acetate has an important metabolic role as a substrate for lipogenesis or energy production and as an effector for gluconeogenesis (Whitton, Rodrigues and Hems, 1979 (Demigné, R6m6sy and Rayssiguier, 1980 Coupled anion transfer could be non-specific for CI-and HC03, but might concern either VFA and HC03 (McNeil, Cummings and James, 1979) (Scholte and Groot, 1975 (Groot, 1975) (Krebs et al, 1974 ;Ozand et al, 1978) and propionate in the ruminant (Demigné and R6m6sy, 1977 …”

Section: Introductionmentioning

confidence: 99%

Origin and utilization of volatile fatty acids in the rat

Rémésy¹,

Demigné²,

Chartier³

1980

Reprod. Nutr. Dévelop.

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“…GS-0976 improve fatty liver but may increase acetyl-CoA content in the liver by inhibition of ACC1/2. In hepatocytes, it has been reported that gluconeogenesis from lactic acid is increased by acetate, which is a substrate for acetyl-CoA, therefore gluconeogenesis could be promoted by increasing acetyl-CoA [45,46]. Furthermore, increased hepatic acetyl-CoA by GS-0976 may have promoted gluconeogenesis and caused increase in plasma glucose and compensatory plasma insulin.…”

Section: Discussionmentioning

confidence: 99%

Acetyl-CoA carboxylase 1 and 2 inhibition ameliorates steatosis and hepatic fibrosis in a MC4R knockout murine model of nonalcoholic steatohepatitis

Matsumoto¹,

Yashiro

Ogino³

et al. 2020

PLoS ONE

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Acetyl-CoA carboxylase (ACC) catalyzes the rate-limiting step in de novo lipogenesis, which is increased in the livers of patients with nonalcoholic steatohepatitis. GS-0976 (firsocostat), an inhibitor of isoforms ACC1 and ACC2, reduced hepatic steatosis and serum fibrosis biomarkers such as tissue inhibitor of metalloproteinase 1 in patients with nonalcoholic steatohepatitis in a randomized controlled trial, although the impact of this improvement on fibrosis has not fully been evaluated in preclinical models. Here, we used Western diet-fed melanocortin 4 receptor-deficient mice that have similar phenotypes to nonalcoholic steatohepatitis patients including progressively developed hepatic steatosis as well as fibrosis. We evaluated the effects of ACC1/2 inhibition on hepatic fibrosis. After the confirmation of significant hepatic fibrosis with a 13-week pre-feeding, GS-0976 (4 and 16 mg/kg/day) treatment for 9 weeks lowered malonyl-CoA and triglyceride content in the liver and improved steatosis, histologically. Furthermore, GS-0976 reduced the histological area of hepatic fibrosis, hydroxyproline content, mRNA expression level of type I collagen in the liver, and plasma tissue metalloproteinase inhibitor 1, suggesting an improvement of hepatic fibrosis. The treatment with GS-0976 was also accompanied by reductions of plasma ALT and AST levels. These data demonstrate that improvement of hepatic lipid metabolism by ACC1/2 inhibition could be a new option to suppress fibrosis progression as well as to improve hepatic steatosis in nonalcoholic steatohepatitis.

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Stimulation by acetate of gluconeogenesis in hepatocyte suspensions

Cited by 11 publications

References 19 publications

Acute effects of ethanol on the perfused rat liver. Studies on lipid and carbohydrate metabolism, substrate cycling and perfusate amino acids

Acute effects of ethanol on the perfused rat liver. Studies on lipid and carbohydrate metabolism, substrate cycling and perfusate amino acids

Origin and utilization of volatile fatty acids in the rat

Acetyl-CoA carboxylase 1 and 2 inhibition ameliorates steatosis and hepatic fibrosis in a MC4R knockout murine model of nonalcoholic steatohepatitis

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