Gene expression of livers from Lpcat3fl/fl and Lpcat3fl/fl Albumin-Cre mice on chow diet
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ABSTRACT: The total abundance of phosphatidylcholine (PC) is known to influence lipoprotein production. However, the role of specific phospholipid species in lipid transport has been difficult to assess due to an inability to selectively manipulate membrane composition in vivo. Here we show that the LXR-regulated phospholipid remodeling enzyme lysophosphatidylcholine acyltransferase 3 (Lpcat3) is a critical determinant of membrane phospholipid composition and lipoprotein production. Mice lacking Lpcat3 in the liver show defects in lipoprotein production. The objective of generating this dataset was to analyze the effects of Lpcat3 loss of function on baseline gene expression in mouse liver. This dataset compares gene expression in Lpcat3fl/fl and Lpcat3fl/fl Albumin-Cre liver samples from 12-week old male mice that were subjected to 6 hr fasting. Each sample contains tissues from 5 mice.
Project description:The total abundance of phosphatidylcholine (PC) is known to influence lipoprotein production. However, the role of specific phospholipid species in lipid transport has been difficult to assess due to an inability to selectively manipulate membrane composition in vivo. Here we show that the LXR-regulated phospholipid remodeling enzyme lysophosphatidylcholine acyltransferase 3 (Lpcat3) is a critical determinant of membrane phospholipid composition and lipoprotein production. Mice lacking Lpcat3 in the liver show defects in lipoprotein production. The objective of generating this dataset was to analyze the effects of Lpcat3 loss of function on gene expression in mouse liver with a western diet challenge. This dataset compares gene expression in Lpcat3fl/fl and Lpcat3fl/fl Albumin-Cre liver samples from 16-week old male mice that were fed a western diet for 9 weeks since 7 weeks old. Each sample contains tissues from 5 mice.
Project description:The total abundance of phosphatidylcholine (PC) is known to influence lipoprotein production. However, the role of specific phospholipid species in lipid transport has been difficult to assess due to an inability to selectively manipulate membrane composition in vivo. Here we show that the LXR-regulated phospholipid remodeling enzyme lysophosphatidylcholine acyltransferase 3 (Lpcat3) is a critical determinant of membrane phospholipid composition and lipoprotein production. Mice lacking Lpcat3 in the liver show defects in lipoprotein production. The objective of generating this dataset was to analyze the effects of Lpcat3 loss of function on baseline gene expression in mouse liver.
Project description:The total abundance of phosphatidylcholine (PC) is known to influence lipoprotein production. However, the role of specific phospholipid species in lipid transport has been difficult to assess due to an inability to selectively manipulate membrane composition in vivo. Here we show that the LXR-regulated phospholipid remodeling enzyme lysophosphatidylcholine acyltransferase 3 (Lpcat3) is a critical determinant of membrane phospholipid composition and lipoprotein production. Mice lacking Lpcat3 in the liver show defects in lipoprotein production. The objective of generating this dataset was to analyze the effects of Lpcat3 loss of function on gene expression in mouse liver with a western diet challenge.
Project description:In pigs, most of the lipogenic activity takes place in liver and the adipose tissue. Moreover, liver is responsible for the production and release of lipoproteins, which transports lipids from the liver to target tissues such as adipose and muscle. In the context of animal production, the amount and composition of lipoprotein have an implication in the accumulation of fat in adipose deposits but also in muscle in the form or intramuscular fat. These two events have consequences in the quality of the carcasses and meat. We have measured the level of liver gene expression in 104 commercial Duroc pigs belonging to two groups with extreme phenotypes for traits strongly related with lipid deposition and composition. This has allowed us to compare the physiological and metabolic implications of selecting for each of these extreme groups. This information has been complemented with genome-wide genotyping data in order to describe the implication of the liver transcriptome in the production traits which encompass the production and marketing of the products with consumer and industry-relevant added-value characteristics. 104 liver samples form pigs belonging to two groups of animals: HIGH group (n=53) had higher carcass, plasma and muscle fat content; LOW group (n=51) had lower carcass, plasma and muscle fat content
Project description:We used microarray to analyze the global gene expression in crypts isolated from wild-type (Lpcat3F/F) and Lpcat3 tamoxifen inducible intestine-specific knockout (Lpcat3F/F, Villin-CreERT2) crypts. Phospholipid remodeling is a critical determinant of membrane composition and function. How membrane phospholipid composition affects tissue stem cell function and tumorigenesis is unknown. Here we demonstrate that Lpcat3-dependent phospholipid remodeling regulates intestinal stem cell (ISC) proliferation and promotes tumorigenesis in intestine. The objective of generating this dataset was to analyze the effects of Lpcat3 loss of function on gene expression in mouse intestine crypts.
Project description:Aberrant concentration, structure and functionality of High Density Lipoprotein (HDL) is associated with many prevalent diseases, including cardiovascular disease and non-alcoholic fatty liver disease (NAFLD). Mice with liver-specific ablation of Hnf4α (H4LivKO) present steatosis and dyslipidemia by mechanisms that are not completely understood. The aim of this study was to explore the role of liver Hnf4α in HDL metabolism and the development of steatosis.
Project description:Liver tissue from Vps33b liver ko (Vps33bfl/fl-AlfpCre) mice is a model of liver disease associated with ARC syndrome, an autosomal recessive inherited metabolic disorder cause by mutations in VPS33B or VIPAS39. ARC is a multisystem disorder, with liver and kidneys affected in particular. Defects in hepatocyte polarity have been identified. Affymetrix arrays were used to characterise the changes in the liver transcriptome when Vps33b is not expressed. Mouse liver tissue, 10 samples in total, 4 from control mice, 6 from ko mice.
Project description:Background and aims: NASH, characterized by inflammation and fibrosis, is emerging as a leading etiology of HCC. Lipidomics analyses in the liver have shown that the levels of polyunsaturated phosphatidylcholine (PC) are decreased in patients with NASH, but the roles of membrane PC composition in the pathogenesis of NASH have not been investigated. Lysophosphatidylcholine acyltransferase 3 (LPCAT3), a phospholipid (PL) remodeling enzyme that produces polyunsaturated PLs, is a major determinant of membrane PC content in the liver. Approach and results: The expression of LPCAT3 and the correlation between its expression and NASH severity were analyzed in human patient samples. We examined the effect of Lpcat3 deficiency on NASH progression using Lpcat3 liver-specific knockout (LKO) mice. RNA sequencing, lipidomics, and metabolomics were performed in liver samples. Primary hepatocytes and hepatic cell lines were used for in vitro analyses. We showed that LPCAT3 was dramatically suppressed in human NASH livers, and its expression was inversely correlated with NAFLD activity score and fibrosis stage. Loss of Lpcat3 in mouse liver promotes both spontaneous and diet-induced NASH/HCC. Mechanistically, Lpcat3 deficiency enhances reactive oxygen species production due to impaired mitochondrial homeostasis. Loss of Lpcat3 increases inner mitochondrial membrane PL saturation and elevates stress-induced autophagy, resulting in reduced mitochondrial content and increased fragmentation. Furthermore, overexpression of Lpcat3 in the liver ameliorates inflammation and fibrosis of NASH. Conclusions: These results demonstrate that membrane PL composition modulates the progression of NASH and that manipulating LPCAT3 expression could be an effective therapeutic for NASH.