title: Chromosome 19 open reading frame 80 is upregulated by thyroid hormone and modulates autophagy and lipid metabolism.
abstract: The thyroid hormone, T 3, regulates cell growth, differentiation and development through binding to the nuclear thyroid hormone receptor (THR), a member of the steroid/TR superfamily of ligand-dependent transcriptional factors. T 3 modulates lipid metabolism in liver, although the detailed molecular mechanisms are unclear at present. Here, by a microarray analysis, we identified a novel chromosome 19 open reading frame 80 (C19orf80) which was activated by T 3. T 3 stimulation led to upregulation of both mRNA and protein levels of C19orf80. Immunofluorescence analysis revealed a vesicle-like pattern of C19orf80 around lipid droplets or within the lysosome-associated compartment in cells. Furthermore, T 3 treatment as well as C19orf80 overexpression specifically activated the autophagic response and lipid metabolism, as observed from lipidated LC3 (LC3-II) and levels of oxygen consumption rate, respectively. Reciprocally, knockdown of C19orf80 obstructed T 3-activated autophagy and lipolysis. Moreover, treatment with autolysosome maturation inhibitors, ammonium chloride and chloroquine, not only suppressed the T 3-activated autophagic process but also lipid metabolism. Our results collectively suggested that T 3 regulates lipid metabolism through a C19orf80-activated autophagic process.
authors.affiliation: Graduate Institute of Biomedical Sciences; College of Medicine; Chang Gung University; Taoyuan, Taiwan.
authors.forename: Yi-Hsin
authors.initials: YH
authors.lastname: Tseng
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Po-Yuan
authors.initials: PY
authors.lastname: Ke
authors.affiliation: Graduate Institute of Biomedical Sciences; College of Medicine; Chang Gung University; Taoyuan, Taiwan.
authors.forename: Chia-Jung
authors.initials: CJ
authors.lastname: Liao
authors.affiliation: Graduate Institute of Biomedical Sciences; College of Medicine; Chang Gung University; Taoyuan, Taiwan.
authors.forename: Sheng-Ming
authors.initials: SM
authors.lastname: Wu
authors.affiliation: Graduate Institute of Biomedical Sciences; College of Medicine; Chang Gung University; Taoyuan, Taiwan.
authors.forename: Hsiang-Cheng
authors.initials: HC
authors.lastname: Chi
authors.affiliation: Graduate Institute of Biomedical Sciences; College of Medicine; Chang Gung University; Taoyuan, Taiwan.
authors.forename: Chung-Ying
authors.initials: CY
authors.lastname: Tsai
authors.affiliation: Graduate Institute of Biomedical Sciences; College of Medicine; Chang Gung University; Taoyuan, Taiwan.
authors.forename: Cheng-Yi
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Graduate Institute of Biomedical Sciences; College of Medicine; Chang Gung University; Taoyuan, Taiwan.
authors.forename: Yang-Hsiang
authors.initials: YH
authors.lastname: Lin
authors.affiliation: Graduate Institute of Biomedical Sciences; College of Medicine; Chang Gung University; Taoyuan, Taiwan; Department of Medical Research; Chang Gung Memorial Hospital; Taoyuan, Taiwan.
authors.forename: Kwang-Huei
authors.initials: KH
authors.lastname: Lin
mesh_terms: D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins; D001343:Autophagy / Q000187:drug effects* / Q000235:genetics; D001483:Base Sequence; D002460:Cell Line; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D055785:Gene Knockdown Techniques; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects* / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008969:Molecular Sequence Data; D036361:Peptide Hormones / Q000235:genetics* / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D013963:Thyroid Hormones / Q000494:pharmacology*; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics; D014284:Triiodothyronine / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects* / Q000235:genetics; D014617:Vacuoles / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure
chemical_list: C576683:ANGPTL8 protein, human; D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins; D036361:Peptide Hormones; D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones; D014284:Triiodothyronine
keywords: autophagy; chromosome 19 open reading frame 80; lipid droplet; lysosome; thyroid hormone