Identifying the role of Acox1 in metabolism and inflammation in non-alcoholic fatty liver disease through mRNA-sequencing.
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ABSTRACT: Purpose: To identify the impact of Acox1 on cellular metabolism and inflammation related to non-alcoholic fatty liver disease, within the context of obesogenic dietary stress. Methods: Hepatic mRNA profiles were obtained in triplicate for control and Acox1Lampe1 mice on chow diet or obesogenic diet. Profiles were generated using the Illumina HiSeq2000, reads that passed quality inspection were processed through the TopHap/Cufflinks pipeline. Results: Approximately 20million reads per sample were aligned to the mm8 mouse genome, using annotations provided by Ensembl. Testing between control and Acox1Lampe1 mice on control and obesogenic diets was performed using a 2-way ANOVA, with a p-value cutoff of 0.05 and FC of 1.5. We observed a significant alteration of hepatic gene expression in Acox1Lampe1 mutant mice, a pattern that was exacerbated by the obesogenic diet. Among significant genes, we observed an enrichment of those known to teb associated with inflammatory responses, leukocyte activation and adhesion, and abnormal liver physiology, regeneration, and development. Conclusion: Through next generation sequencing of hepatic tissues from control and Acox1Lampe1 mutant mice on control and obesogenic diets, we demonstrate that Acox1 regulates both metabolism and inflammation, the interplay of which correlates with increased hepatocellular damage and impared hepatic mitochondrial function.
Project description:This dataset contains proteomic data from mice with high or low weight gain in response to a high fat diet. Both host and microbial proteins are present. In the supplemental, there are also tables and supplementary files that can be used for replicating the bioinformatic analysis.
Abstract:
Consumption of refined high-fat, low-fiber diets promotes development of obesity and its associated consequences. While genetics play an important role in dictating susceptibility to such obesogenic diets, mice with nearly uniform genetics exhibit marked heterogeneity in their extent of obesity in response to such diets. This suggests non-genetic determinants play a role in diet-induced obesity. Hence, we sought to identify parameters that predict, and/or correlate with, development of obesity in response to an obesogenic diet. We assayed behavior, metabolic parameters, inflammatory markers/cytokines, microbiota composition, and the fecal metaproteome, in a cohort of mice (n=50) prior to, and the 8 weeks following, administration of an obesogenic high-fat low-fiber diet. Neither behavioral testing nor quantitation of inflammatory markers broadly predicted severity of diet-induced obesity. Although, the small subset of mice that exhibited basal elevations in serum IL-6 (n=5) were among the more obese mice in the cohort. While fecal microbiota composition changed markedly in response to the obesogenic diet, it lacked the ability to predict which mice were relative prone or resistant to obesity. In contrast, fecal metaproteome analysis revealed functional and taxonomic differences among the proteins associated with proneness to obesity. Targeted interrogation of microbiota composition data successfully validated the taxonomic differences seen in the metaproteome. While future work will be needed to determine the breadth of applicability of these associations to other cohorts of animals and humans, this study nonetheless highlights the potential power of gut microbial proteins to predict and perhaps impact development of obesity.
Project description:The target of this project is to investigate the effect of ACOX1 knockout in liver Gene expression profiling analysis were performed using data obtained from RNA-seq of two genotypes mice liver
Project description:To investigate the role of ACOX1, we knocked down ACOX1 by shRNA in HK-2 cell lines and detected differential genes. We then performed gene expression profiling analysis using data obtained from RNA-seq of 2 different cells.
Project description:Hepatic gene expression analysis in mice fed control diet or diets supplemented with 1% Fraction 1 (haxane) or Fraction 2 (methanol) of Boswellia Serrata Keywords: other
Project description:De novo lipogenesis (DNL) has been implicated in the development and progression of hepatic liver steatosis. Hepatic DNL is strongly influenced by dietary macronutrient composition with diets high in carbohydrate increasing DNL and diets high in fat decreasing DNL. The enzymes in the core DNL pathway have been well characterised however less is known about proteins that play accessory or regulatory roles in DNL. In the current study, we associate measured rates of hepatic DNL and liver fat content with abundance of liver proteins from liquid chromatography mass spectrometry in mice to identify known and uncharacterised proteins that may have a role in DNL. Male C57BL/6J mice were fed either a standard chow diet a semi-purified high starch diet or a high fat diet. Both semi-purified diets resulted in increased body weight, fat mass and liver triglyceride content compared to chow-fed mice while hepatic DNL was increased in the high starch fed mice and decreased in the high fat fed mice. Proteomic analysis was carried out on the livers of these mice and proteins were identified that associated with either the rate of DNL or triglyceride content in the liver. There was no overlap between DNL and triglyceride associated proteins. We identify novel proteins associated with DNL that are involved in taurine metabolism, which suggests a link between these pathways. Further analysis identified proteins that are differentially regulated when comparing a non-purified chow diet to either of the semi-purified diets to provide a set of proteins that are regulated by the degree of dietary complexity alone. Finally, we compared the liver proteome between 4 week-fed and 30-week diet-fed mice and found remarkable similarity suggesting that the majority of diet-regulated proteins change early in response to differing dietary components.
Project description:Hepatic gene expression analysis in mice fed control diet or diets supplemented with 1% Fraction 1 (haxane) or Fraction 2 (methanol) of Boswellia Serrata.
Project description:To gain insight into the mechanism(s) by which obesogenic diet caused decreased uterine contractility at term, we collected uterine tissue from mice fed either a control (CON) or an obesogenic (DIO) diet at day 18.5 of pregnancy and performed RNA sequencing.
Project description:The multitude of obesogenic diets used in rodent studies is enormous and thus hardly manageable. Since standardization is missing and it is presumed that individual compositions provoke individual effects, the choice of quality, quantity and combination of diet ingredients seems to be crucial for the outcome and interpretation of obesity studies. Therefore, the present study was conducted to compare the effects of three commonly used obesogenic diets on selected parameters. Besides basic phenotypic and metabolic characterization, one main aspect was a comparative liver proteome analysis. As expected, the obtained results picture differentiated consequences mainly depending on fat source and/or fat- and sugar quantity. By confirming the general presumption that the choice of nutritional composition is a pivotal factor, the present findings demonstrate that a conscious selection is indispensable for obtaining reliable and sound results in obesity research.In conclusion, we strongly recommend a thorough selection of the appropriate obesogenic diet prior to an experiment and in consideration of the individual research question.
Project description:Analysis of effect of luteolin on lipid metabolism at gene expression level. The hypothesis tested in the present study was that luteolin treatment with obesogenic diet suppressed the hepatic lipogenesis pathways. Conversely, in adipose tissue, luteolin stimulated the lipogenesis pathway and it also simultaneously increased the expression of genes controlling lipolysis and TCA cycle. Results provide important information about the effect on diet-induced obesity and its metabolic complications. Total RNA of liver and adipose tissues was obtained from normal diet, high-fat diet and luteolin added high-fat diet-fed mice and mRNA expression-associated with lipid metabolism was measured.