Regulation of plasma triglyceride partitioning by adipose-derived ANGPTL4 in mice.
Regulation of plasma triglyceride partitioning by adipose-derived ANGPTL4 in mice.
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DOI：
10.1038/s41598-021-87020-5
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发表时间：
2021-04-12
影响因子：
4.6
通讯作者：
Davies BSJ
中科院分区：
文献类型：
--
作者：
Spitler KM;Shetty SK;Cushing EM;Sylvers-Davie KL;Davies BSJ
血浆甘油三酯水平升高与代谢性疾病有关。血管生成素样蛋白4（ANGPTL4）通过抑制脂蛋白脂酶（LPL）调节血浆甘油三酯水平。我们的目的是研究脂肪细胞特异性ANGPTL4缺陷在高脂饮食喂养小鼠中的作用。脂肪细胞特异性ANGPTL 4缺陷小鼠喂食高脂肪饮食（脂肪中60% kCal）12周或6个月。我们进行了血浆代谢测量，甘油三酯清除和摄取测定，LPL活性测定，并评估葡萄糖稳态。缺乏脂肪细胞ANGPTL4的小鼠重现了全身ANGPTL4缺乏的甘油三酯表型，包括脂肪LPL活性增加、血浆甘油三酯水平降低和脂肪组织甘油三酯摄取增加。当喂食高脂饮食（HFD）时，这些小鼠继续显示增强的脂肪LPL活性，并且最初具有改善的葡萄糖和胰岛素敏感性。然而，在HFD治疗6个月后，葡萄糖稳态的改善在很大程度上消失了。此外，尽管脂肪LPL活性水平较高，但与同窝对照相比，缺乏脂肪细胞ANGPTL4的小鼠在慢性高脂喂养后不再具有增加的甘油三酯摄取到脂肪中。这些观察结果表明，长期高脂喂养后，LPL不再是甘油三酯输送到脂肪细胞的速率限制。我们的结论是，虽然脂肪细胞来源的ANGPTL4是正常饮食条件下血浆甘油三酯水平和甘油三酯分配的重要调节剂，但其作用在慢性高脂喂养后减弱。
Elevated plasma triglyceride levels are associated with metabolic disease. Angiopoietin-like protein 4 (ANGPTL4) regulates plasma triglyceride levels by inhibiting lipoprotein lipase (LPL). Our aim was to investigate the role of adipocyte-specific deficiency of ANGPTL4 in mice during high fat diet feeding. Adipocyte-specific ANGPTL4 deficient mice were fed a high fat diet (60% kCal from fat) for either 12 weeks or 6 months. We performed plasma metabolic measurements, triglyceride clearance and uptake assays, LPL activity assays, and assessed glucose homeostasis. Mice lacking adipocyte ANGPTL4 recapitulated the triglyceride phenotypes of whole-body ANGPTL4 deficiency, including increased adipose LPL activity, lower plasma triglyceride levels, and increased uptake of triglycerides into adipose tissue. When fed a high fat diet (HFD), these mice continued to display enhanced adipose LPL activity and initially had improved glucose and insulin sensitivity. However, after 6 months on HFD, the improvements in glucose homeostasis were largely lost. Moreover, despite higher adipose LPL activity levels, mice lacking adipocyte ANGPTL4 no longer had increased triglyceride uptake into adipose compared to littermate controls after chronic high-fat feeding. These observations suggest that after chronic high-fat feeding LPL is no longer rate-limiting for triglyceride delivery to adipocytes. We conclude that while adipocyte-derived ANGPTL4 is an important regulator of plasma triglyceride levels and triglyceride partitioning under normal diet conditions, its role is diminished after chronic high-fat feeding.
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影响因子：
2.2
作者：
Bailetti, D.;Bertoccini, L.;Baroni, M. G.
通讯作者：
Baroni, M. G.
影响因子：
29
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影响因子：
8.2
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通讯作者：
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影响因子：
4.8
作者：
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通讯作者：
Olivecrona, T
影响因子：
4.8
作者：
Chi, Xun;Shetty, Shwetha K.;Davies, Brandon S. J.
通讯作者：
Davies, Brandon S. J.