title: Angiopoietin-like 3 regulates hepatocyte proliferation and lipid metabolism in zebrafish.
abstract: Loss-of-function mutations in angiopoietin-like 3 (ANGPTL3) cause familial hypobetalipoproteinemia type 2 (FHBL2) in humans. ANGPTL3 belongs to the angiopoietin-like family, the vascular endothelial growth factor family that is structurally similar to angiopoietins and is known for a regulator of lipid and glucose metabolism, although it is unclear how mutations in ANGPTL3 lead to defect in liver development in the vertebrates. We report here that angptl3 is primarily expressed in the zebrafish developing liver and that morpholino (MO) knockdown of Angptl3 reduces the size of the developing liver, which is caused by suppression of cell proliferation, but not by enhancement of apoptosis. However, MO knockdown of Angptl3 did not alter angiogenesis in the developing liver. Additionally, disruption of zebrafish Angptl3 elicits the hypocholesterolemia phenotype that is characteristic of FHBL2 in humans. Together, our findings propose a novel role for Angptl3 in liver cell proliferation and maintenance during zebrafish embryogenesis. Finally, angptl3 morphants will serve as a good model for understanding the pathophysiology of FHBL2.
authors.affiliation: Department of Biological Sciences, Sookmyung Women's University, Seoul, Republic of Korea; Department of Biology, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: So-Hyun
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Biology, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Ju-Hoon
authors.initials: JH
authors.lastname: So
authors.affiliation: Department of Biology, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Hyun-Taek
authors.initials: HT
authors.lastname: Kim
authors.affiliation: Department of Biology, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Jung-Hwa
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Department of Biology, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Mi-Sun
authors.initials: MS
authors.lastname: Lee
authors.affiliation: Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju, Republic of Korea; School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Seok-Yong
authors.initials: SY
authors.lastname: Choi
authors.affiliation: Department of Biology, Chungnam National University, Daejeon, Republic of Korea. Electronic address: zebrakim@cnu.ac.kr.
authors.forename: Cheol-Hee
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Sookmyung Women's University, Seoul, Republic of Korea. Electronic address: minkim@sookmyung.ac.kr.
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Kim
mesh_terms: D000091303:Angiopoietin-Like Protein 3; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D049109:Cell Proliferation; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D006995:Hypobetalipoproteinemias / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000033:anatomy & histology / Q000196:embryology* / Q000378:metabolism; D009929:Organ Size; D015027:Zebrafish / Q000033:anatomy & histology / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C000589046:ANGPTL3 protein, zebrafish; D000091303:Angiopoietin-Like Protein 3; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D029961:Zebrafish Proteins
keywords: Angiogenesis; Angiopoietin-like 3; Angptl3; Hypobetalipoproteinemia; Liver; Zebrafish