Dataset Information

Metabolomic profiling in liver of adiponectin-knockout mice uncovers lysophospholipid metabolism as an important target of adiponectin action.

ABSTRACT: Adiponectin mediates anti-diabetic effects via increasing hepatic insulin sensitivity and direct metabolic effects. In the present study, we conducted a comprehensive and unbiased metabolomic profiling of liver tissue from AdKO (adiponectin-knockout) mice, with and without adiponectin supplementation, fed on an HFD (high-fat diet) to derive insight into the mechanisms and consequences of insulin resistance. Hepatic lipid accumulation and insulin resistance induced by the HFD were reduced by adiponectin. The HFD significantly altered levels of 147 metabolites, and bioinformatic analysis indicated that one of the most striking changes was the profile of increased lysophospholipids. These changes were largely corrected by adiponectin, at least in part via direct regulation of PLA2 (phospholipase A2) as palmitate-induced PLA2 activation was attenuated by adiponectin in primary hepatocytes. Notable decreases in several glycerolipids after the HFD were reversed by adiponectin, which also corrected elevations in several diacyglycerol and ceramide species. Our data also indicate that stimulation of ?-oxidation of fatty acids by the HFD is enhanced by adiponectin. In conclusion, this metabolomic profiling approach in AdKO mice identified important targets of adiponectin action, including PLA2, to regulate lysophospholipid metabolism and ?-oxidation of fatty acids.

SUBMITTER: Liu Y

PROVIDER: S-EPMC4828338 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Metabolomic profiling in liver of adiponectin-knockout mice uncovers lysophospholipid metabolism as an important target of adiponectin action.

Liu Ying Y Sen Sanjana S Wannaiampikul Sivaporn S Palanivel Rengasamy R Hoo Ruby L C RL Isserlin Ruth R Bader Gary D GD Tungtrongchitr Rungsunn R Deshaies Yves Y Xu Aimin A Sweeney Gary G

The Biochemical journal 20150427 1

Adiponectin mediates anti-diabetic effects via increasing hepatic insulin sensitivity and direct metabolic effects. In the present study, we conducted a comprehensive and unbiased metabolomic profiling of liver tissue from AdKO (adiponectin-knockout) mice, with and without adiponectin supplementation, fed on an HFD (high-fat diet) to derive insight into the mechanisms and consequences of insulin resistance. Hepatic lipid accumulation and insulin resistance induced by the HFD were reduced by adip ...[more]

PMID: 25915851

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Project description:BACKGROUND:The N-terminal prohormone of brain natriuretic peptide (NT-proBNP) is an important biomarker for the diagnosis of heart failure. Apart from this and only recently recognized, NT-proBNP levels associate with higher HDL- and lower LDL-cholesterol levels comprising a favorable blood lipid profile. To further examine this observation, the lipoprotein profile in relation to NT-proBNP was examined in-depth by proton nuclear magnetic resonance spectroscopy (1H-NMR). We complemented this investigation with a state-of-the-art untargeted metabolomics approach. METHODS:Lipoprotein particles were determined by 1H-NMR spectroscopy in 872 subjects without self-reported diabetes from the population-based Study of Health in Pomerania (SHIP)-TREND with available NT-proBNP measurements. Comprehensive metabolomics data for plasma and urine samples were obtained. Linear regression models were performed to assess the associations between serum concentrations of NT-proBNP and the metabolites/lipoprotein particles measured in plasma or urine. RESULTS:An increase in serum NT-proBNP was associated with a benefical lipoprotein profile, including a decrease in VLDL, IDL and LDL-particles along with an increase in large HDL particles. These findings were replicated in a second independent cohort. Serum concentrations of NT-proBNP showed significant inverse associations with seven plasma metabolites while associations with 39 urinary metabolites, mostly comprising amino acids and related intermediates, were identified. Mediation analyses revealed adiponection as mediating factor for the associations observed with lipoproteins particles. CONCLUSIONS:Most of the metabolic changes associated with NT-proBNP implicate significant influence on the blood lipid profile besides vasodilatory and the diuretic action of BNP signaling. Our data suggest that the more favorable lipoprotein profile as associated with elevated NT-proBNP concentrations in mainly cardiac healthy individuals might relate to adiponectin signaling indicating even indirect cardio-protective effects for NT-proBNP.

Project description:Pmk1, a highly conserved pathogenicity-related mitogen-activated protein kinase (MAPK) in pathogenic fungi, is phosphorylated and activated by MAP2K and acts as a global regulator of fungal infection and invasive growth by modulating downstream targets. However, the hierarchical CcPmk1 regulatory network in Cytospora chrysosperma, the main causal agent of canker disease in many woody plant species, is still unclear. In this study, we analyzed and compared the phosphoproteomes and metabolomes of ΔCcPmk1 and wild-type strains and identified pathogenicity-related downstream targets of CcPmk1. We found that CcPmk1 could interact with the downstream homeobox transcription factor CcSte12 and affect its phosphorylation. In addition, the ΔCcSte12 displayed defective phenotypes that were similar to yet not identical to that of the ΔCcPmk1 and included significantly reduced fungal growth, conidiation, and virulence. Remarkably, CcPmk1 could phosphorylate proteins translated from a putative secondary metabolism-related gene cluster, which is specific to C. chrysosperma, and the phosphorylation of several peptides was completely abolished in the ΔCcPmk1. Functional analysis of the core gene (CcPpns1) in this gene cluster revealed its essential roles in fungal growth and virulence. Metabolomic analysis showed that amino acid metabolism and biosynthesis of secondary metabolites, lipids, and lipid-like molecules significantly differed between wild type and ΔCcPmk1. Importantly, most of the annotated lipids and lipid-like molecules were significantly downregulated in the ΔCcPmk1 compared to the wild type. Collectively, these findings suggest that CcPmk1 may regulate a small number of downstream master regulators to control fungal growth, conidiation, and virulence in C. chrysosperma. IMPORTANCE Understanding the pathogenic mechanisms of plant pathogens is a prerequisite to developing effective disease-control methods. The Pmk1 MAPK is highly conserved among phytopathogenic fungi and acts as a global regulator of fungal pathogenicity by modulating downstream transcription factors or other components. However, the regulatory network of CcPmk1 from C. chrysosperma remains enigmatic. The present data provide evidence that the core pathogenicity regulator CcPmk1 modulates a few downstream master regulators to control fungal virulence in C. chrysosperma through transcription or phosphorylation and that CcPmk1 may be a potential target for disease control.

Dataset Information

Metabolomic profiling in liver of adiponectin-knockout mice uncovers lysophospholipid metabolism as an important target of adiponectin action.

Publications

Metabolomic profiling in liver of adiponectin-knockout mice uncovers lysophospholipid metabolism as an important target of adiponectin action.

Similar Datasets

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