Lupin protein influences the expression of hepatic genes involved in fatty acid synthesis and triacylglycerol hydrolysis of adult rats

To assess the effect of lupin protein on concentrations of lipids in plasma lipoproteins and liver and hepatic mRNA concentrations of genes involved in lipid metabolism, adult rats were fed egg albumin-based diets containing either lupin protein fromLupinus albusor casein (50 g/kg) supplemented (hypercholesterolaemic) or not (normolipaemic) with a cholesterol–cholate mixture for 20 d. Lupin protein compared with casein lowered the concentrations of TAG in liver (P < 0·01) and circulating VLDL + chylomicrons (P < 0·05) of hypercholesterolaemic rats, but not of normolipaemic rats. Hepatic mRNA concentrations of genes involved in fatty acid synthesis such as sterol regulatory element-binding protein-1c, glucose-6-phosphate dehydrogenase, fatty acid synthase, stearoyl-CoA desaturase-1 and acyl-CoA:glycerol-3-phosphate acyltransferase were lower and mRNA concentrations of lipoprotein lipase, hepatic lipase and apoA5 involved in TAG hydrolysis were higher in rats fed lupin protein than in rats fed casein. These effects were stronger in hypercholesterolaemic rats than in normolipaemic rats. Hypercholesterolaemic rats fed the lupin protein had higher liver cholesterol concentrations (P < 0·01) and lower levels of LDL-cholesterol (P < 0·05) than rats fed casein. No effect of lupin protein was observed on cholesterol concentration in VLDL + chylomicrons and HDL and hepatic mRNA concentrations of genes involved in cholesterol and bile acid metabolism. In conclusion, the present study shows that lupin protein has hypotriacylglycerolaemic action possibly via down regulation of fatty acid synthesis genes and up regulation of genes involved in TAG hydrolysis. Alterations in cholesterol metabolism could not be explained on the basis of mRNA data.

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Liver Bile Acid Changes in Mouse Models of Alzheimer’s Disease

International Journal of Molecular Sciences ◽

10.3390/ijms22147451 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7451

Author(s):

Harpreet Kaur ◽

Drew Seeger ◽

Svetlana Golovko ◽

Mikhail Golovko ◽

Colin Kelly Combs

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Bile Acid ◽

Bile Acids ◽

Cholesterol Metabolism ◽

Amyloid Β ◽

Acid Synthesis ◽

Bile Acid Synthesis ◽

Liver Cholesterol ◽

Bile Acid Metabolism

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive cognitive impairment. It is hypothesized to develop due to the dysfunction of two major proteins, amyloid-β (Aβ) and microtubule-associated protein, tau. Evidence supports the involvement of cholesterol changes in both the generation and deposition of Aβ. This study was performed to better understand the role of liver cholesterol and bile acid metabolism in the pathophysiology of AD. We used male and female wild-type control (C57BL/6J) mice to compare to two well-characterized amyloidosis models of AD, APP/PS1, and AppNL-G-F. Both conjugated and unconjugated primary and secondary bile acids were quantified using UPLC-MS/MS from livers of control and AD mice. We also measured cholesterol and its metabolites and identified changes in levels of proteins associated with bile acid synthesis and signaling. We observed sex differences in liver cholesterol levels accompanied by differences in levels of synthesis intermediates and conjugated and unconjugated liver primary bile acids in both APP/PS1 and AppNL-G-F mice when compared to controls. Our data revealed fundamental deficiencies in cholesterol metabolism and bile acid synthesis in the livers of two different AD mouse lines. These findings strengthen the involvement of liver metabolism in the pathophysiology of AD.

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The Involvement of PPARs in the Peculiar Energetic Metabolism of Tumor Cells

10.20944/preprints201805.0034.v1 ◽

2018 ◽

Author(s):

Andrea Antonosante ◽

Michele d'Angelo ◽

Vanessa Castelli ◽

Mariano Catanesi ◽

Dalila Iannotta ◽

...

Keyword(s):

Fatty Acid ◽

Cancer Cells ◽

Fatty Acid Synthesis ◽

Cancer Metabolism ◽

Cholesterol Metabolism ◽

Aerobic Glycolysis ◽

Acid Synthesis ◽

Energetic Metabolism ◽

Metabolic Alterations ◽

Long Time

Energy homeostasis is crucial for cell fate since all cellular activities are strongly dependent on the balance between catabolic and anabolic pathways. In particular, metabolic and energetic modulation has been reported in cancer cells long time ago, but have been neglected for a long time. Instead, during the past 20 years a recovery of the study of cancer metabolism has led to better consider metabolic alterations in tumors. Cancer cells must adapt their metabolism to meet the energetic and biosynthetic demands that accompany rapid growth of the primary tumor and colonization of distinct metastatic sites. They are largely dependent on aerobic glycolysis for their energy production and also are associated with increased fatty acid synthesis and increased rates of glutamine utilization. Emerging evidence has shown that therapeutic resistance to cancer treatment may arise due to deregulation in glucose metabolism, fatty acid synthesis, and glutamine utilization. Cancer cells exhibit a series of metabolic alterations induced by mutations leading to gain-of-function of oncogenes and loss-of-function of tumor suppressor genes that include increased glucose consumption, reduced mitochondrial respiration, increased reactive oxygen species generation and cell death resistance, all of which responsible for cancer progression. Cholesterol metabolism is also altered in cancer cells and supports uncontrolled cell growth. In this context, we review the roles of PPARs transcription factors, master regulators of cellular energetic metabolism, in the control and deregulation of energetic homeostasis observed in cancer. We highlight the different contribution of the different PPAR isotypes in different cancers and the differential control of their transcription in the different cancer cells.

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Effect of diabetes on cholesterol and fatty acid synthesis in the rat aorta

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1960.198.1.25 ◽

1960 ◽

Vol 198 (1) ◽

pp. 25-28 ◽

Cited By ~ 39

Author(s):

Daniel W. Foster ◽

Marvin D. Siperstein

Keyword(s):

Fatty Acid ◽

Fatty Acid Synthesis ◽

Cholesterol Synthesis ◽

Acid Synthesis ◽

Rat Aorta ◽

Diabetic Rats ◽

Liver Cholesterol ◽

Hepatic Cholesterol ◽

Hepatic Cholesterol Synthesis ◽

Normal Controls

The synthesis of cholesterol and fatty acids from acetate-1-C14 was studied in the aortas and livers of 42 diabetic rats and their normal controls. Hepatic cholesterol synthesis was significantly increased in 13, decreased in 13, and unchanged in 16 of the 42 animals. Fatty acid synthesis was depressed in the liver in 39 of the 42 diabetic rats. Aortic cholesterogenesis was increased in only 2 of the 13 aortas from the same rats showing elevated hepatic cholesterol synthesis. Fatty acid synthesis was depressed in 21 of 42 aortas from the diabetic group. It is concluded, therefore, that the aorta is relatively resistant to stimulation of cholesterol synthesis by diabetes even when hepatic cholesterol synthesis in the same animal is elevated. Lipogenesis on the other hand is commonly depressed in the aorta as well as the liver. Cholesterol was purified through dibrominization and both normal and diabetic aortas were shown to be capable of carrying cholesterol synthesis to completion.

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Fatty acid synthesis in the regenerating liver of the rat

Biochemical Journal ◽

10.1042/bj1700001 ◽

1978 ◽

Vol 170 (1) ◽

pp. 1-8 ◽

Cited By ~ 30

Author(s):

C D Gove ◽

D A Hems

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Partial Hepatectomy ◽

Fatty Acid Synthesis ◽

De Novo ◽

Plasma Concentrations ◽

Liver Glycogen ◽

Acid Synthesis ◽

Liver Cholesterol ◽

Regenerating Liver

1. Synthesis de novo of fatty acids in the rat liver, measured per g wet wt. of tissue, was increased by a factor of about two, between 1 and 4 days after partial hepatectomy, compared with rates in sham-operated control rat livers. 2. There were no associated changes in the rates of liver cholesterol synthesis or of adipose-tissue fatty acid synthesis in rats after partial hepatectomy, compared with rates in sham-operated rats. 3. In regenerating livers, perfused under three different conditions, there was no alteration in the capacity for fatty acid synthesis compared with that of control rats. 4. The increased synthesis of fatty acids in regenerating liver was associated with insignificant increases in plasma concentrations of tricylglycerols and free fatty acids, with a decrease in content of liver glycogen, and with no change in hepatic activity of acetyl-CoA carboxylase. 5. The accelerated rate of synthesis of fatty adids in regenerating liver appears not to be due to any intrinsic alteration in hepatic capacity for fatty acid synthesis, but it may be caused by the continuous action on liver of unidentified circulating factors.

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