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Integrated metabolomics reveals altered lipid metabolism in adipose tissue in a model of extreme longevity.

ABSTRACT: Adipose tissue plays an essential role in metabolic health. Ames dwarf mice are exceptionally long-lived and display metabolically beneficial phenotypes in their adipose tissue, providing an ideal model for studying the intersection between adipose tissue and longevity. To this end, we assessed the metabolome and lipidome of adipose tissue in Ames dwarf mice. We observed distinct lipid profiles in brown versus white adipose tissue of Ames dwarf mice that are consistent with increased thermogenesis and insulin sensitivity, such as increased cardiolipin and decreased ceramide concentrations. Moreover, we identified 5-hydroxyeicosapentaenoic acid (5-HEPE), an ?-3 fatty acid metabolite, to be increased in Ames dwarf brown adipose tissue (BAT), as well as in circulation. Importantly, 5-HEPE is increased in other models of BAT activation and is negatively correlated with body weight, insulin resistance, and circulating triglyceride concentrations in humans. Together, these data represent a novel lipid signature of adipose tissue in a mouse model of extreme longevity.

SUBMITTER: Darcy J

PROVIDER: S-EPMC7732932 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Integrated metabolomics reveals altered lipid metabolism in adipose tissue in a model of extreme longevity.

Darcy Justin J Fang Yimin Y McFadden Samuel S Lynes Matthew D MD Leiria Luiz O LO Dreyfuss Jonathan M JM Bussburg Valerie V Tolstikov Vladimir V Greenwood Bennett B Narain Niven R NR Kiebish Michael A MA Bartke Andrzej A Tseng Yu-Hua YH

GeroScience 20200706 6

Adipose tissue plays an essential role in metabolic health. Ames dwarf mice are exceptionally long-lived and display metabolically beneficial phenotypes in their adipose tissue, providing an ideal model for studying the intersection between adipose tissue and longevity. To this end, we assessed the metabolome and lipidome of adipose tissue in Ames dwarf mice. We observed distinct lipid profiles in brown versus white adipose tissue of Ames dwarf mice that are consistent with increased thermogenes ...[more]

PMID: 32632845

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Project description:Depression is a common comorbidity in Parkinson's disease (PD) but is underdiagnosed. We aim to investigate the altered metabolic pathways of Parkinson's disease-related depression (PDD) in plasma and to identify potential biomarkers for clinical diagnosis. Consecutive patients with PD were recruited, clinically assessed, and patients with PDD identified. Fasting plasma samples were collected from 99 patients and differentially expressed metabolites and proteins between patients with PDD and PD were identified using non-targeted liquid chromatography-mass spectrometry (LC-MS)-based metabolomics and tandem mass tag (TMT)-based proteomics analysis, followed by an integrated analysis. Based on the above results, enzyme-linked immune sorbent assay (ELISA) tests were then performed to identify potential biomarkers for PDD. In clinics, patients with PDD suffered less hypertension and had lower serum low-density lipoprotein cholesterol and apolipoprotein B levels when compared to the other patients with PD. A total of 85 differentially expressed metabolites were identified in metabolomics analysis. These metabolites were mainly lipids and lipid-like molecules, involved in lipid and glucose metabolic pathways. According to proteomics analysis, 17 differentially expressed proteins were identified, and 12 metabolic pathways were enriched, which were predominantly related to glucose metabolism. Integrated analysis indicated that altered lipid and glucose metabolism in PDD may induce cellular injury through oxidative stress. Additionally, plasma levels of several proteins were confirmed to be significantly altered and correlated with depressive severity. NOTCH2 may be a potential blood biomarker for PDD, with an optimal cut-off point of 0.91 ng/ml, a sensitivity value of 95.65%, and a specificity value of 81.58%. Depressive symptoms are associated with lipid and glucose metabolism in patients with PD and NOTCH2 may be a potential blood biomarker for the clinical diagnosis of PDD.

Dataset Information

Integrated metabolomics reveals altered lipid metabolism in adipose tissue in a model of extreme longevity.

Publications

Integrated metabolomics reveals altered lipid metabolism in adipose tissue in a model of extreme longevity.

Similar Datasets

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