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Betaine affects muscle lipid metabolism via regulating the fatty acid uptake and oxidation in finishing pig.

ABSTRACT: BACKGROUND:Betaine affects fat metabolism in animals, but the specific mechanism is still not clear. The purpose of this study was to investigate possible mechanisms of betaine in altering lipid metabolism in muscle tissue in finishing pigs. METHODS:A total of 120 crossbred gilts (Landrace × Yorkshire × Duroc) with an average initial body weight of 70.1 kg were randomly allotted to three dietary treatments. The treatments included a corn-soybean meal basal diet supplemented with 0, 1250 or 2500 mg/kg betaine. The feeding experiment lasted 42 d. RESULTS:Betaine addition to the diet significantly increased the concentration of free fatty acids (FFA) in muscle (P < 0.05). Furthermore, the levels of serum cholesterol and high-density lipoprotein cholesterol were decreased (P < 0.05) and total cholesterol content was increased in muscle (P < 0.05) of betaine fed pigs. Experiments on genes involved in fatty acid transport showed that betaine increased expression of lipoprotein lipase(LPL), fatty acid translocase/cluster of differentiation (FAT/CD36), fatty acid binding protein (FABP3) and fatty acid transport protein (FATP1) (P < 0.05). The abundance of fatty acid transport protein and fatty acid binding protein were also increased by betaine (P < 0.05). As for the key factors involved in fatty acid oxidation, although betaine supplementation didn't affect the level of carnitine and malonyl-CoA, betaine increased mRNA and protein abundance of carnitine palmitransferase-1(CPT1) and phosphorylated-AMPK (P < 0.05). CONCLUSIONS:The results suggested that betaine may promoted muscle fatty acid uptake via up-regulating the genes related to fatty acid transporter including FAT/CD36, FATP1 and FABP3. On the other hand, betaine activated AMPK and up-regulated genes related to fatty acid oxidation including PPAR? and CPT1. The underlying mechanism regulating fatty acid metabolism in pigs supplemented with betaine is associated with the up-regulation of genes involved in fatty acid transport and fatty acid oxidation.

SUBMITTER: Li S

PROVIDER: S-EPMC5580292 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Betaine affects muscle lipid metabolism via regulating the fatty acid uptake and oxidation in finishing pig.

Li Sisi S Wang Haichao H Wang Xinxia X Wang Yizhen Y Feng Jie J

Journal of animal science and biotechnology 20170901

<h4>Background</h4>Betaine affects fat metabolism in animals, but the specific mechanism is still not clear. The purpose of this study was to investigate possible mechanisms of betaine in altering lipid metabolism in muscle tissue in finishing pigs.<h4>Methods</h4>A total of 120 crossbred gilts (Landrace × Yorkshire × Duroc) with an average initial body weight of 70.1 kg were randomly allotted to three dietary treatments. The treatments included a corn-soybean meal basal diet supplemented with 0 ...[more]

PMID: 28883917

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Project description:Methods: We performed mRNA sequence analysis by deep sequencing, in triplicate, using Illumina HiSeq to assess the impact of PHLPP1 knockdown in regulating gene expression in RAW 264.7 cells treated with/without OxLDL. The transcriptome libraries were constructed using the NEB adapters and were sequenced on at 150 nucleotide read length using the paired-end chemistry. The raw reads were subjected to Adapter and low-quality reads removal by Trimmomatic -0.36v. The raw reads were subjected to contamination [structural RNA / low complexity sequences] removal by mapping with bowtie 2-2.2.1. The decontaminated data set was mapped to the mouse genome. Reads mapping to gene list were counted using feature count module of sub reads package. The read counts were normalized in DESeq2-3.5, and subject to differential expression analysis. Differentially expressed genes were selected based on log2-ratio change with p-value <0.05 (Student’s t-test, unpaired). Hierarchical clustering was performed with the programs Cluster (uncentered correlation; average linkage clustering) and Treeview. Results: To gain a deeper understanding of the role of PHLPP1 in lipid metabolism in macrophages, we performed mRNA Seq analysis to assess the gene expression changes in a mouse macrophage cell line. The experiment has been carried out in triplicates. Alignment of the reads showed 97% alignment to the reference mouse genome. Identification of the differentially expressed genes were then carried out by DESeq2 version 1.2.10 with stringent criteria (FDR <0.05% with 2 fold up and down regulation) which reveals in control treated vs. control (121-down, 396-Up), Test vs. Control - (326-down, 569 Up) and Test treated vs. control treated (1314-down, 1328 up) of DEG to be altered in expression respectively. Inference: RNA-seq analysis revealed that PHLPP1 knockdown parallel with OxLDL treatment resulted in diminished expression profile of cholesterol biosynthesis and lipid metabolism genes.

Project description:Background Defects in the renal fatty acid ?-oxidation pathway have been implicated in the development of renal fibrosis. Our group has developed a therapeutic vaccine targeting PCSK9 (proprotein convertase subtilisin/kexin type 9), named PCSK9Q?-003. In this study, we investigated the potential effectiveness of the PCSK9Q?-003 vaccine on hypercholesterolemia with renal fibrosis. Methods and Results The low-density lipoprotein receptor+/- male mice fed with a high-cholesterol (1%) Western diet were randomly assigned into 4 groups: the sham group (or the control group), the phosphate-buffered saline group, the Q? virus-like particles group and the PCSK9Q?-003 vaccine group. Mice of the PCSK9Q?-003 group were injected with the PCSK9Q?-003 vaccine (100 ?g/time) every 2 or 4 weeks. The mice were administered with either unilateral ureteral obstruction for 2 weeks or N-nitro-l-arginine methyl ester (50 mg/kg per day) for 6 weeks to establish a renal fibrosis model. Compared with the other 3 groups, the PCSK9Q?-003 vaccine obviously decreased total cholesterol and low-density lipoprotein cholesterol in low-density lipoprotein receptor+/- mice with hypercholesterolemia. Compared with the phosphate-buffered saline and Q? virus-like particles groups, the PCSK9Q?-003 vaccine improved hepatic steatosis and renal function. Histology analysis showed that the PCSK9Q?-003 vaccine significantly ameliorated renal lipid accumulation and renal fibrosis. Moreover, the PCSK9Q?-003 vaccine obviously upregulated the expression of low-density lipoprotein receptor, very-low-density lipoprotein receptor, sterol-regulatory element binding protein 2, and fatty acid ?-oxidation-related factors, and ameliorated renal fibrosis-related molecules both in the unilateral ureteral obstruction and N-nitro-l-arginine methyl ester models. Conclusions This study suggested that the PCSK9Q?-003 vaccine improved renal lipid accumulation and renal fibrosis by regulating fatty acid ?-oxidation, which may provide a promising method for treating hypercholesterolemia with renal fibrosis.

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Betaine affects muscle lipid metabolism via regulating the fatty acid uptake and oxidation in finishing pig.

Publications

Betaine affects muscle lipid metabolism via regulating the fatty acid uptake and oxidation in finishing pig.

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