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Association between betatrophin/ANGPTL8 and non-alcoholic fatty liver disease: animal and human studies

Authors
 Yong-ho Lee  ;  Sang-Guk Lee  ;  Chan Joo Lee  ;  Soo Hyun Kim  ;  Young-Mi  ;  Mi Ra Yoon  ;  Byung Hun Jeon  ;  Jae Hyuk Lee  ;  Byung-Wan Lee  ;  Eun Seok Kang  ;  Hyun Chul Lee  ;  Bong-Soo Cha 
Citation
 Scientific Reports, Vol.6 : 24013, 2016 
Journal Title
 Scientific Reports 
ISSN
 2045-2322 
Issue Date
2016
MeSH
Angiopoietin-like Proteins ; Angiopoietins/blood* ; Animals ; Body Mass Index ; Case-Control Studies ; Cell Proliferation ; Comorbidity ; Diabetes Complications/blood ; Diabetes Complications/diagnosis ; Endoplasmic Reticulum/metabolism ; Enzyme-Linked Immunosorbent Assay ; Female ; Hep G2 Cells ; Hepatocytes/metabolism ; Humans ; Liver/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease/blood* ; Obesity/blood ; Obesity/complications ; Palmitates/chemistry ; Peptide Hormones/blood* ; Prospective Studies ; Real-Time Polymerase Chain Reaction ; Tunicamycin/chemistry
Abstract
Betatrophin/angiopoietin-like protein 8 (ANGPTL8) is a liver-secreted protein recently identified as a potent stimulator of beta cell proliferation in mice. However, it is unclear how betatrophin is regulated in humans with non-alcoholic fatty liver disease (NAFLD). We investigated the role of betatrophin in mice and in humans with and without NAFLD. Serum betatrophin levels were examined by ELISA in 164 subjects, including 96 patients with NAFLD. Levels were significantly elevated in subjects with NAFLD compared with controls (1.301 ± 0.617 vs. 0.900 ± 0.574 μg/L, P < 0.001), even after stratification by diabetic or obesity status. Circulating betatrophin positively correlated with obesity or glycemic indices, liver enzyme profiles, and NAFLD status, and was confirmed by multivariate regression analyses (β = 0.195, P = 0.040). However, when including insulin resistance index in the model, the significant association between betatrophin level and NAFLD was diminished due to a mediation effect of insulin resistance on this relationship. Palmitate or tunicamycin increased betatrophin expression in HepG2 cells, while a chemical chaperone blocked its induction. Hepatic expression of betatrophin was elevated in mice with NAFLD including db/db or ob/ob mice and mice with a high-fat or methionine-choline deficient diet. In conclusion, circulating betatrophin was increased in mice and humans with NAFLD and its expression was induced by endoplasmic reticulum stress in hepatocytes (Clinical trial no. NCT02285218).
Files in This Item:
T201601311.pdf Download
DOI
10.1038/srep24013
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
7. Others (기타) > Dept. of Health Promotion (건강의학과) > 1. Journal Papers
Yonsei Authors
Kang, Eun Seok(강은석) ORCID logo https://orcid.org/0000-0002-0364-4675
Lee, Byung Wan(이병완) ORCID logo https://orcid.org/0000-0002-9899-4992
Lee, Sang-Guk(이상국) ORCID logo https://orcid.org/0000-0003-3862-3660
Lee, Yong Ho(이용호) ORCID logo https://orcid.org/0000-0002-6219-4942
Lee, Chan Joo(이찬주) ORCID logo https://orcid.org/0000-0002-8756-409X
Lee, Hyun Chul(이현철)
Cha, Bong Soo(차봉수) ORCID logo https://orcid.org/0000-0003-0542-2854
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/146785
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