Transcript and metabolite analysis of the effects of tamoxifen in rat liver reveals inhibition of fatty acid synthesis in the presence of hepatic steatosis

The in vitro effect of alloxan and insulin on the synthesis of cholesterol and fatty acids from 1-C14-sodium acetate by rat liver homogenates has been examined. Alloxan caused a reduction in the incorporation of acetate into cholesterol, fatty acids, and C14O2, but an increase in the oxygen consumption and carbon dioxide production. The addition of insulin to homogenates caused a reduction in cholesterol synthesis but an increase in fatty acid synthesis both for normal and diabetic animals. Homogenates from thyrotoxic rats exhibited a marked reduction in cholesterol synthesis when compared with normal animals. C14O2 production by homogenates from starved rats was appreciably lower than for those from normal animals. With this exception no appreciable difference was found in the oxygen uptake, carbon dioxide, or C14O2 production in homogenates from normal, starved, thyroxine-treated, or diabetic animals. Synthesized cholesterol was found to be located principally in the particulate matter of the homogenates after they had been incubated with 1-C14-sodium acetate. Homogenates from starved rats showed no greater tendency to degrade preformed cholesterol during incubation than did those from normal rats.

Download Full-text

Effect of Dietary Soybean Phospholipid and Fats Differing in the Degree of Unsaturation on Fatty Acid Synthesis and Oxidation in Rat Liver.

Journal of Nutritional Science and Vitaminology ◽

10.3177/jnsv.41.635 ◽

1995 ◽

Vol 41 (6) ◽

pp. 635-645 ◽

Cited By ~ 10

Author(s):

Yearul KABIR ◽

Takashi IDE

Keyword(s):

Fatty Acid ◽

Rat Liver ◽

Fatty Acid Synthesis ◽

Acid Synthesis ◽

Degree Of Unsaturation ◽

Soybean Phospholipid

Download Full-text

Acetyl-CoA carboxylase inhibition by ND-630 reduces hepatic steatosis, improves insulin sensitivity, and modulates dyslipidemia in rats

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1520686113 ◽

2016 ◽

Vol 113 (13) ◽

pp. E1796-E1805 ◽

Cited By ~ 122

Author(s):

Geraldine Harriman ◽

Jeremy Greenwood ◽

Sathesh Bhat ◽

Xinyi Huang ◽

Ruiying Wang ◽

...

Keyword(s):

Fatty Acid ◽

Liver Disease ◽

Insulin Sensitivity ◽

Fatty Liver ◽

Hepatic Steatosis ◽

Fatty Acid Synthesis ◽

Fatty Liver Disease ◽

Acid Synthesis ◽

Acid Oxidation ◽

Acetyl Coa Carboxylase

Simultaneous inhibition of the acetyl-CoA carboxylase (ACC) isozymes ACC1 and ACC2 results in concomitant inhibition of fatty acid synthesis and stimulation of fatty acid oxidation and may favorably affect the morbidity and mortality associated with obesity, diabetes, and fatty liver disease. Using structure-based drug design, we have identified a series of potent allosteric protein–protein interaction inhibitors, exemplified by ND-630, that interact within the ACC phosphopeptide acceptor and dimerization site to prevent dimerization and inhibit the enzymatic activity of both ACC isozymes, reduce fatty acid synthesis and stimulate fatty acid oxidation in cultured cells and in animals, and exhibit favorable drug-like properties. When administered chronically to rats with diet-induced obesity, ND-630 reduces hepatic steatosis, improves insulin sensitivity, reduces weight gain without affecting food intake, and favorably affects dyslipidemia. When administered chronically to Zucker diabetic fatty rats, ND-630 reduces hepatic steatosis, improves glucose-stimulated insulin secretion, and reduces hemoglobin A1c (0.9% reduction). Together, these data suggest that ACC inhibition by representatives of this series may be useful in treating a variety of metabolic disorders, including metabolic syndrome, type 2 diabetes mellitus, and fatty liver disease.

Download Full-text