Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA111907 | ENA |
REPOSITORIES: ENA
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Project description:Hepatic metabolic derangements are key components in the development of fatty liver, insulin resistance, and atherosclerosis. SIRT1, a NAD+-dependent protein deacetylase, is an important regulator of energy homeostasis in response to nutrient availability. Here we demonstrate that hepatic SIRT1 regulates fatty acid metabolism by positively regulating PPAR-alpha. Hepatocyte-specific deletion of SIRT1 impairs PPAR-alpha signaling and decreased fatty acid beta-oxidation in the liver. When challenged with a high-fat diet, liver-specific SIRT1 knockout mice develop hepatic steatosis, hepatic inflammation, and endoplasmic reticulum stress. Taken together, our data indicate that SIRT1 plays a vital role in the regulation of hepatic lipid homeostasis.
2009-04-07 | GSE14921 | GEO
Project description:The ketogenic diet has been successful in promoting weight loss among patients that have struggled with weight gain. This is due to the cellular switch in metabolism that utilizes liver-derived ketone bodies for the primary energy source rather than glucose. Fatty acid transport protein 2 (FATP2) is highly expressed in liver, small intestine, and kidney where it functions in both the transport of exogenous long chain fatty acids (LCFA) and in the activation to CoA thioesters of very long chain fatty acids (VLCFA). We have completed a multi-omic study of FATP2-null (Fatp2-/-) mice maintained on a ketogenic diet (KD) or paired control diet (CD), with and without a 24-hour fast (KD-fasted and CD-fasted) to address the impact of deleting FATP2 under high-stress conditions. Control (wt/wt) and Fatp2-/- mice were maintained on their respective diets for 4-weeks. Afterwards, half the population was sacrificed while the remaining were fasted for 24-hours prior to sacrifice. We then performed paired-end RNA-sequencing on the whole liver tissue to investigate differential gene expression. The differentially expressed genes mapped to ontologies such as the metabolism of amino acids and derivatives, fatty acid metabolism, protein localization, and components of the immune system’s complement cascade, and were supported by the proteome and histological staining.
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Project description:We identified the gene Far2, encoding the fatty acyl-coA reductase 2, to be associated with mesangial matrix expansion (MME) in the mouse (PMID: 24009241). In order to verify this association we obtained the C57BL/6N-Far2tm2a(KOMP)Wtsi/2J (JR#018805) strain from The Jackson Laboratory's KOMP2 program and compared this strain to it's control strain (C57BL/6N) for several renal characteristics. At 6 months of age the knockout mice have a significantly better kidney function (measured as glomerular filtration rate) but the MME is at a comparable level. However, as MME increases in the control strain at 12 months of age, MME does not increase in the knockout until 18 months of age. In order to explore changes at the gene expression level, we compared RNA sequence reads from 6-month old kidneys. Our analysis showed a decrease of RNA expression for several tubular damage markers (NGAL, KIM-1) and an increase in several genes in the fatty acid metabolism pathway.
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