Project description:Data acquired for conjugated bile acids with amino acids analysis of human fecal samples by targeted LC-MS. These samples are a part of a study investigating a new BSH function as an amine N-acyl transferase that conjugates amines to form bacterial bile acid amidates (BBAAs).
Project description:Samples-WT Basal condition primary cortex cells; WT B27 Starved-Primary cortex cells starved overnight without B27 supplement media. WT AA Starved-Primary cortex cell starved without amino acid for 2 hours. WT AA Refed-Primary cortex cell refed for 1 hour after amino acid starvation. KO Basal-SLC38 Knockout Primary cortex cells starved overnight without B27 supplement media. KO B27 Starved-SLC38 Knockout Primary cortex cell starved without amino acid for 2 hours. KO AA starved-SLC38 Knockout Primary cortex cell refed for 1 hour after amino acid starvation. KO AA Refed-SLC38 Knockout Primary cortex cell refed for 1 hour after amino acid starvation.
Project description:full title: A mitochondrial long-chain fatty acid oxidation defect in a mouse model leads to dysregulation of plasma long-chain acylcarnitines, dysregulation of plasma amino acids, and an increased reliance on glucocorticoid signaling to maintain euglycemia during fasting. [liver] The liver is a major source of energy substrates during metabolic stress: fasting, prolonged exercise, febrile illness. Fasting-induced hypoglycemia is a characteristic feature of FAO disorders including very long chain acyl-CoA dehydrogenase (VLCAD) deficiency (VLCADD). However, the pathophysiological mechanisms that underlie the diversity of clinical presentation of FAO dysfunction are not known. Here, we investigated the transcriptional response in liver tissue to the FAO defect in a model of VLCADD: the long-chain acyl-CoA dehydrogenase (LCAD) knockout (KO) mouse. We found that differentially expressed genes from the liver were associated with molecular networks annotated for fatty acid oxidation and cholesterol biosynthesis from population-based networks.
Project description:Nudix hydrolase 7 (NUDT7) is a peroxisomal (acyl-)CoA-degrading enzyme that is highly expressed in the liver. We previously showed that liver-specific NUDT7 overexpression affects peroxisomal lipid metabolism, but does not prevent the increase in total liver CoA levels that occurs with fasting. Herein, we show that deletion of Nudt7 alters the composition of the hepatic acyl-CoA pool in mice fed a low fat diet, but only in males fed a western diet does the lack of NUDT7 increase total liver CoA levels. This effect is driven by the accumulation of medium-chain dicarboxylic acyl-CoAs, which are products of the oxidation of dicarboxylic fatty acids in the peroxisomes. We also show that, under conditions of increased cholesterol intake and elevated bile acid synthesis, Nudt7 deletion increases the production of tauro-muricholic acids, decreasing the hydrophobicity index of the intestinal bile acid pool and increasing fecal cholesterol excretion. Collectively, our findings reveal a key role for NUDT7 in the regulation of the final products of bile acid synthesis and dicarboxylic fatty acid oxidation
Project description:A mitochondrial long-chain fatty acid oxidation defect leads to dysregulation of plasma long-chain acyl carnitines, dysregulation of plasma amino acids, and an increased reliance on glucocorticoid signaling to maintain euglycemia during fasting. [muscle] Skeletal muscle tissue relies on products of fatty acid oxidation (FAO) during conditions of metabolic stress: fasting, prolonged exercise, febrile illness. Fasting-induced hypoglycemia and rhabdomyolysis are characteristic features of FAO disorders including very long chain acyl-CoA dehydrogenase (VLCAD) deficiency (VLCADD). However, the pathophysiological mechanisms that underlie the connection between FAO dysfunction and skeletal muscle dysfunction are not known. Here, we investigated the transcriptional response in skeletal muscle tissue (gastrocnemius) to the FAO defect in a model of VLCADD: the long-chain acyl-CoA dehydrogenase (LCAD) knockout (KO) mouse. We found that differentially expressed genes in the muscle were associated with molecular networks annotated for the cellular response to starvation from population-based models. To validate the association between the starvation response and FAO, we pharmacologically inhibited both glucocorticoid signaling and FAO in a model of fasting and observed that mice depleted in both pathways lost less weight during fasting and became hypoglycemic. These findings implicate glucocorticoid signaling as a candidate modifier of the cellular response to starvation in muscle tissue in the context of FAO disorders including VLCADD.
Project description:Interventions: experimental group :PD-1 Knockout Engineered T Cells
Primary outcome(s): Number of participants with Adverse Events and/or Dose Limiting Toxicities as a Measure of Safety and tolerability of dose of PD-1 Knockout T cells using Common Terminology Criteria for Adverse Events (CTCAE v4.0) in patients
Study Design: historical control
Project description:Atlantic salmon can synthesize polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (20:5n-3), arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3) via activities of very long chain fatty acyl elongases (elovls) and fatty acyl desaturases (fads), albeit to a limited degree. Understanding molecular mechanisms of PUFA biosynthesis and regulation is a pre-requisite for sustainable use of vegetable oils in aquafeeds as current sources of fish oils are unable to meet increasing demands for omega-3 PUFAs. By generating CRISPR-mediated elovl2 knockout, we have shown that elovl2 is crucial for multi-tissue synthesis of 22:6n-3 in vivo and endogenously synthesized PUFAs are important for transcriptional regulation of lipogenic genes in Atlantic salmon. The elovl2 knockouts showed reduced levels of 22:6n-3 and accumulation of 20:5n-3 and docosapentaenoic acid (22:5n-3) in the liver, brain and white muscle, suggesting inhibition of elongation. Additionally, elovl2-knockout salmon showed accumulation of 20:4n-6 in the brain and white muscle. The impaired synthesis of 22:6n-3 induced hepatic expression of sterol regulatory element binding protein-1 (srebp-1), fatty acid synthase-b, Δ6fad-a, Δ5fad and elovl5. Our study demonstrates key roles of elovl2 at two penultimate steps of PUFA synthesis in vivo and suggests Srebp-1 as a main regulator of PUFA synthesis in Atlantic salmon.
Project description:A knockout clone has been generated for both FAM50A and FAM50B; knockout of the other gene is then performed and the transcriptome is analysed to look at the effect of dual gene loss.