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论文题目: Fasting and Feeding Signals Control the Oscillatory Expression of Angptl8 to Modulate Lipid Metabolism
英文论文题目: Fasting and Feeding Signals Control the Oscillatory Expression of Angptl8 to Modulate Lipid Metabolism
第一作者: Dang, FB; Wu, R; Wang, PF; Wu, YT; Azam, MS; Xu, Q; Chen, YQ; Liu, Y
英文第一作者: Dang, FB; Wu, R; Wang, PF; Wu, YT; Azam, MS; Xu, Q; Chen, YQ; Liu, Y
联系作者: Liu, Y (reprint author), Chinese Acad Sci, Univ Chinese Acad Sci, Key Lab Nutr & Metab, Inst Nutr Sci,Shanghai Inst Biol Sci, 320 Yueyang Rd, Shanghai 200031, Peoples R China.
英文联系作者: Liu, Y (reprint author), Chinese Acad Sci, Univ Chinese Acad Sci, Key Lab Nutr & Metab, Inst Nutr Sci,Shanghai Inst Biol Sci, 320 Yueyang Rd, Shanghai 200031, Peoples R China.
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发表年度: 2016
卷: 6
期:
页码: 36926
摘要: Emerging evidence implies a key role of angiopoietin-like protein 8 (Angptl8) in the metabolic transition between fasting and feeding, whereas much less is known about the mechanism of its own expression. Here we show that hepatic Angptl8 is rhythmically expressed, which involving the liver X receptor alpha (LXR alpha) and glucocorticoid receptor (GR) modulation during feeding and fasting periods, respectively. In addition, Angptl8 mRNA is very unstable, which contributes to the nature of its daily rhythmicity by rapidly responding to fasting/feeding transition. To explore its pathological function in dexamethasone (DEX)-induced fatty liver, we reversed its suppression by glucocorticoids through adenoviral delivery of Angptl8 gene in mouse liver. Surprisingly, hepatic overexpression of Angptl8 dramatically elevated plasma triglyceride (TG) and non-esterified fatty acid (NEFA) levels in DEX-treated mice, suggesting a metabolic interaction between Angptl8 and glucocorticoid signaling. Moreover, intracellular hepatic Angptl8 is implicated in the regulation of lipid homeostasis by the experiments with ectopic expression of a nonsecreted Angptl8 mutant (Delta 25-Angptl8). Altogether, our data demonstrate the molecular mechanism of the diurnal rhythm of Angptl8 expression regulated by glucocorticoid signaling and LXRa pathway, and provide new evidence to understand the role of Angptl8 in maintaining plasma TG homeostasis.
英文摘要: Emerging evidence implies a key role of angiopoietin-like protein 8 (Angptl8) in the metabolic transition between fasting and feeding, whereas much less is known about the mechanism of its own expression. Here we show that hepatic Angptl8 is rhythmically expressed, which involving the liver X receptor alpha (LXR alpha) and glucocorticoid receptor (GR) modulation during feeding and fasting periods, respectively. In addition, Angptl8 mRNA is very unstable, which contributes to the nature of its daily rhythmicity by rapidly responding to fasting/feeding transition. To explore its pathological function in dexamethasone (DEX)-induced fatty liver, we reversed its suppression by glucocorticoids through adenoviral delivery of Angptl8 gene in mouse liver. Surprisingly, hepatic overexpression of Angptl8 dramatically elevated plasma triglyceride (TG) and non-esterified fatty acid (NEFA) levels in DEX-treated mice, suggesting a metabolic interaction between Angptl8 and glucocorticoid signaling. Moreover, intracellular hepatic Angptl8 is implicated in the regulation of lipid homeostasis by the experiments with ectopic expression of a nonsecreted Angptl8 mutant (Delta 25-Angptl8). Altogether, our data demonstrate the molecular mechanism of the diurnal rhythm of Angptl8 expression regulated by glucocorticoid signaling and LXRa pathway, and provide new evidence to understand the role of Angptl8 in maintaining plasma TG homeostasis.
刊物名称: SCIENTIFIC REPORTS
英文刊物名称: SCIENTIFIC REPORTS
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学科: Multidisciplinary Sciences
英文学科: Multidisciplinary Sciences
影响因子: 4.259
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论文类别: Article
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