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Publications (177) View all
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Article: Structural studies on archaeal phytanyl-ether lipids isolated from membranes of extreme halophiles by linear ion-trap multiple-stage tandem mass spectrometry with electrospray ionization.
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ABSTRACT: The structures of archaeal glycerophospholipids and glycolipids are unique in that they consist of phytanyl substituents ether linked to the glycerol backbone, imparting stability to the molecules. In this contribution, we described multiple-stage linear ion-trap combined with high resolution mass spectrometry toward structural characterization of this lipid family desorbed as lithiated adduct ions or as the [M-H](-) and [M-2H](2-) ions by ESI. MS(n) on various forms of the lithiated adduct ions yielded rich structurally informative ions leading to complete structure identification of this lipid family, including the location of the methyl branches of the phytanyl chain. By contrast, structural information deriving from MS(n) on the [M-H](-) and [M-2H](2-) ions is not complete. The fragmentation pathways in an ion-trap, including unusual internal loss of glycerol moiety and internal loss of hexose found for this lipid family were proposed. This mass spectrometric approach provides a simple tool to facilitate confident characterization of this unique lipid family.Analytica chimica acta 04/2013; 771:73-85. · 4.31 Impact Factor -
Article: Selective hepatic insulin resistance in mice heterozygous for a mitochondrial trifunctional protein defect.
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ABSTRACT: Earlier reports suggest a link between mitochondrial dysfunction and development of hepatic insulin resistance. Here we used a murine model heterozygous (HET) for a mitochondrial trifunctional protein (MTP) gene defect to determine if a primary defect in mitochondrial long-chain fatty acid oxidation disrupts hepatic insulin action.Hyperinsulinemic-euglycemic clamps and signaling studies were performed for assessment of whole-body and hepatic insulin resistance/signaling. In addition, hepatic fatty acid oxidation and hepatic insulin action were assessed in vitro utilizing primary hepatocytes isolated from HET and wild-type (WT) mice. In both hepatic mitochondria and isolated primary hepatocytes, heterozygosity of MTP caused a ∼50% reduction in mitochondrial fatty acid oxidation, a significantly impaired glucose disposal during the insulin clamp,and a markedly lower insulin-stimulated suppression of hepatic glucose production. HET mice also exhibited impaired insulin signaling, with increased hepatic phosphorylation of IRS2 (ser731) and reduced Aktphosphorylation (ser473)in both hepatic tissue and isolated primary hepatocytes. Assessment of insulin-stimulated FOXO1/phospho-FOXO1protein content and PEPCK/G6Pase mRNA expression did not reveal differences between HET and WT mice. However, insulin-induced phosphorylation of GSK3β was significantly blunted in HET mice. Hepatic insulin resistance was associated with an increased methylation status of the catalytic subunit of protein phosphatase 2A (PP2A-C), but was not associated with differences in hepatic DAG content, activated PKC-ε, IKK-β, JNK, or phospho-JNK protein contents. Surprisingly, hepatic ceramides were significantly lower in the HET mice compared with WT. CONCLUSIONS: Our data document that a primary defect in mitochondrial fatty acid β-oxidation causes hepatic insulin resistance selective to hepatic glycogen metabolism that is associated with elevated methylated PP2A-C, but independent of other mechanisms commonly considered to be responsible for insulin resistance. (HEPATOLOGY 2013.).Hepatology 01/2013; · 11.66 Impact Factor -
Dataset: jms2033
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Dataset: AB-2011
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Dataset: JMS3070
