整合代谢组学揭示了一种极端长寿模型中脂肪组织中脂质代谢的改变。
Integrated metabolomics reveals altered lipid metabolism in adipose tissue in a model of extreme longevity.
机构信息
Joslin Diabetes Center, Section on Integrative Physiology and Metabolism, Harvard Medical School, Boston, MA, USA.
Department of Internal Medicine, Geriatric Research, Southern Illinois University School of Medicine, Springfield, IL, USA.
出版信息
Geroscience. 2020 Dec;42(6):1527-1546. doi: 10.1007/s11357-020-00221-0. Epub 2020 Jul 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 thermogenesis and insulin sensitivity, such as increased cardiolipin and decreased ceramide concentrations. Moreover, we identified 5-hydroxyeicosapentaenoic acid (5-HEPE), an ω-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.
脂肪组织在代谢健康中起着至关重要的作用。Ames 矮鼠异常长寿，并在其脂肪组织中表现出有益代谢的表型，为研究脂肪组织与长寿之间的交叉点提供了理想的模型。为此，我们评估了 Ames 矮鼠脂肪组织的代谢组和脂质组。我们观察到 Ames 矮鼠棕色脂肪组织与白色脂肪组织之间存在明显不同的脂质谱，这与产热和胰岛素敏感性增加一致，例如心磷脂浓度增加和神经酰胺浓度降低。此外，我们发现 5-羟二十碳五烯酸（5-HEPE），一种 ω-3 脂肪酸代谢物，在 Ames 矮鼠棕色脂肪组织（BAT）以及循环中增加。重要的是，5-HEPE 在其他 BAT 激活模型中增加，并且与人体中体重、胰岛素抵抗和循环甘油三酯浓度呈负相关。总之，这些数据代表了一种新型的长寿小鼠模型中脂肪组织的脂质特征。
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