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

 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 
 Scientific Reports, Vol.6 : 24013-24013, 2016 
Journal Title
 Scientific Reports 
Issue Date
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
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).
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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
Yonsei Authors
강은석(Kang, Eun Seok) ORCID logo https://orcid.org/0000-0002-0364-4675
이병완(Lee, Byung Wan) ORCID logo https://orcid.org/0000-0002-9899-4992
이상국(Lee, Sang-Guk) ORCID logo https://orcid.org/0000-0003-3862-3660
이용호(Lee, Yong Ho) ORCID logo https://orcid.org/0000-0002-6219-4942
이찬주(Lee, Chan Joo) ORCID logo https://orcid.org/0000-0002-8756-409X
이현철(Lee, Hyun Chul)
차봉수(Cha, Bong Soo) ORCID logo https://orcid.org/0000-0003-0542-2854
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