iPla2β deficiency in mice fed with MCD diet does not correct the defect of phospholipid remodeling but attenuates hepatocellular injury via an inhibition of lipid uptake genes.

07:00 EST 5th February 2019 | BioPortfolio

Summary of "iPla2β deficiency in mice fed with MCD diet does not correct the defect of phospholipid remodeling but attenuates hepatocellular injury via an inhibition of lipid uptake genes."

Group VIA calcium-independent phospholipase A2 (iPla2β) is among modifier genes of non-alcoholic fatty liver disease which leads to non-alcoholic steatohepatitis (NASH). Consistently, iPla2β deletion protects hepatic steatosis and obesity in genetic ob/ob and obese mice chronically fed with high-fat diet by replenishing the loss of hepatic phospholipids (PL). As mouse feeding with methionine- and choline-deficient (MCD) diet is a model of lean NASH, we tested whether iPla2β-null mice could still be protected since PL syntheses are disturbed. MCD-diet feeding of female wild-type for 5 weeks induced hepatic steatosis with a severe reduction of body and visceral fat weights concomitant with a decrease of hepatic phosphatidylcholine. These parameters were not altered in MCD-fed iPla2β-null mice. However, iPla2β deficiency attenuated MCD-induced elevation of serum transaminase activities and hepatic expression of fatty-acid translocase Cd36, fatty-acid binding protein-4, peroxisome-proliferator activated receptorγ, and HDL-uptake scavenger receptor B type 1. The reduction of lipid uptake genes was consistent with a decrease of hepatic esterified and unesterified fatty acids and cholesterol esters. On the contrary, iPla2β deficiency under MCD did not have any effects on inflammasomes and pro-inflammatory markers but exacerbated hepatic expression of myofibroblast α-smooth muscle actin and vimentin. Thus, without any rescue of PL loss, iPla2β inactivation attenuated hepatocellular injury in MCD-induced NASH with a novel mechanism of lipid uptake inhibition. Taken together, we have shown that iPla2β mediates hepatic steatosis and lipotoxicity in hepatocytes in both obese and lean NASH, but elicits exacerbated liver fibrosis in lean NASH likely by affecting other cell types.


Journal Details

This article was published in the following journal.

Name: Biochimica et biophysica acta. Molecular and cell biology of lipids
ISSN: 1879-2618


DeepDyve research library

PubMed Articles [11153 Associated PubMed Articles listed on BioPortfolio]

Group VIA phospholipase A2 deficiency in mice chronically fed with high-fat-diet attenuates hepatic steatosis by correcting a defect of phospholipid remodeling.

A defect of hepatic remodeling of phospholipids (PL) is seen in non-alcoholic fatty liver disease and steatohepatitis (NASH) indicating pivotal role of PL metabolism in this disease. The deletion of g...

ADAMTS5 deficiency in mice does not affect cardiac function.

The aggrecanase ADAMTS5 (A Disintegrin and Metalloproteinase with ThromboSpondin type 1 motifs, member 5) and the cleavage of its substrate versican have been implicated in the development of heart va...

Methionine-Choline Deprivation Impairs Adult Hippocampal Neurogenesis in C57BL/6 Mice.

Methionine and choline, which are essential nutrients for mammalian animals, are important for cell composition, as metabolic factors, and for the synthesis of other biochemical compounds for cell met...

Phytosterol containing diet increases plasma and whole body concentration of phytosterols in apoE-KO but not in LDLR-KO mice.

Phytosterol metabolism is unknown in the hypercholesterolemia of genetic origin. We investigated the metabolism of phytosterols in a cholesterol-free, phytosterol-containing standard diet in hyperchol...

Dietary cholesterol is essential to mast cell activation and associated obesity and diabetes in mice.

Mast cell (MC) deficiency in Kit mice and inhibition with disodium chromoglycate (DSCG) or ketotifen reduced obesity and diabetes in mice on a high-cholesterol (1.25%) Western diet. Yet, Kit-independe...

Clinical Trials [4968 Associated Clinical Trials listed on BioPortfolio]

Pyruvate Kinase Deficiency Epidemiological Study

Pyruvate kinase deficiency (PKD) is the most common red cell glycolytic enzyme defect causing hereditary non-spherocytic hemolytic anemia, caused by mutations in the PKLR gene. The main go...

A Pilot Study of Intermittent Calorie Restriction in Multiple Sclerosis

Experimental studies of the experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, indicate that the number of calories fed to mice prevent EAE and are also ...

A Randomized Controlled Trial of Nicotinamide Supplementation in Early Parkinson's Disease: the NOPARK Study

NOPARK is a double-blinded randomized controlled trial that studies nicotinamide supplementation in early Parkinson's disease. Parkinson's disease (PD) is a major cause of death and disab...

Powder Topical Rifampicin on Reducing Infections After Neural Tube Defect Surgery in Infants

The correct timing and technique of neural tube defect (NTD) repairs significantly decreases the morbidity and mortality of NTD cases. However, infections related to the surgery are still ...

The Effect of Triheptanoin on Fatty Acid Oxidation and Exercise Tolerance in Patients With Glycogenoses

The aim of this study is to investigate the effect of 14 days of treatment with the dietary oil-supplement Triheptanoin on fat metabolism and exercise tolerance in patients with Phosphofru...

Medical and Biotech [MESH] Definitions

A nutritional condition produced by a deficiency of VITAMIN B 12 in the diet, characterized by megaloblastic anemia. Since vitamin B 12 is not present in plants, humans have obtained their supply from animal products, from multivitamin supplements in the form of pills, and as additives to food preparations. A wide variety of neuropsychiatric abnormalities is also seen in vitamin B 12 deficiency and appears to be due to an undefined defect involving myelin synthesis. (From Cecil Textbook of Medicine, 19th ed, p848)

A nutritional condition produced by a deficiency of VITAMIN D in the diet, insufficient production of vitamin D in the skin, inadequate absorption of vitamin D from the diet, or abnormal conversion of vitamin D to its bioactive metabolites. It is manifested clinically as RICKETS in children and OSTEOMALACIA in adults. (From Cecil Textbook of Medicine, 19th ed, p1406)

A nutritional condition produced by a deficiency of THIAMINE in the diet, characterized by anorexia, irritability, and weight loss. Later, patients experience weakness, peripheral neuropathy, headache, and tachycardia. In addition to being caused by a poor diet, thiamine deficiency in the United States most commonly occurs as a result of alcoholism, since ethanol interferes with thiamine absorption. In countries relying on polished rice as a dietary staple, BERIBERI prevalence is very high. (From Cecil Textbook of Medicine, 19th ed, p1171)

A nutritional condition produced by a deficiency of VITAMIN B 6 in the diet, characterized by dermatitis, glossitis, cheilosis, and stomatitis. Marked deficiency causes irritability, weakness, depression, dizziness, peripheral neuropathy, and seizures. In infants and children typical manifestations are diarrhea, anemia, and seizures. Deficiency can be caused by certain medications, such as isoniazid.

The late onset form of MULTIPLE CARBOXYLASE DEFICIENCY (deficiency of the activities of biotin-dependent enzymes propionyl-CoA carboxylase, methylcrotonyl-CoA carboxylase, and PYRUVATE CARBOXYLASE) due to a defect or deficiency in biotinidase which is essential for recycling BIOTIN.

Quick Search


DeepDyve research library

Relevant Topics

Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...

Hepatology is the study of liver, gallbladder, biliary tree, and pancreas, and diseases associated with them. This includes viral hepatitis, alcohol damage, cirrhosis and cancer. As modern lifestyles change, with alcoholism and cancer becoming more promi...

Searches Linking to this Article