title: Fasting and Feeding Signals Control the Oscillatory Expression of Angptl8 to Modulate Lipid Metabolism.
abstract: 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 (LXRα) 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 (Δ25-Angptl8). Altogether, our data demonstrate the molecular mechanism of the diurnal rhythm of Angptl8 expression regulated by glucocorticoid signaling and LXRα pathway, and provide new evidence to understand the role of Angptl8 in maintaining plasma TG homeostasis.
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road Shanghai, 200031, China.
authors.forename: Fabin
authors.initials: F
authors.lastname: Dang
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road Shanghai, 200031, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wu
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road Shanghai, 200031, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Wang
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road Shanghai, 200031, China.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road Shanghai, 200031, China.
authors.forename: Md Shofiul
authors.initials: MS
authors.lastname: Azam
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, NanGang District, Harbin, 150001, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road Shanghai, 200031, China.
authors.forename: Yaqiong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road Shanghai, 200031, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D047369:Chromatin Immunoprecipitation; D003907:Dexamethasone / Q000494:pharmacology; D005215:Fasting; D005230:Fatty Acids, Nonesterified / Q000032:analysis; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000378:metabolism; D000071518:Liver X Receptors / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D020218:Response Elements; D047488:Retinoid X Receptors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014280:Triglycerides / Q000032:analysis
chemical_list: C000595899:ANGPTL8 protein, mouse; D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins; D005230:Fatty Acids, Nonesterified; D005938:Glucocorticoids; D000071518:Liver X Receptors; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D047488:Retinoid X Receptors; D014280:Triglycerides; D003907:Dexamethasone