Elevated serum transaminase activities were associated with increased serum levels of iron regulatory hormone hepcidin and hyperferritinemia risk.
Iron imbalance is a feature of liver damage. However, the biological correlation of serum hepcidin, a key regulator of iron homeostasis, with liver malfunction is undefined. To this end, we piloted the Chinese population studies to address whether hepcidin is linked to liver functionality. The serum hepcidin, ferritin, alanine transaminase, aspartate transaminase, gamma-glutamyltransferase and bilirubin were examined in two independent Chinese cohorts consisted of 3455 individuals. After adjustment for sex, age, body mass index, smoking habits, drinking categories and diabetic status, a positive association between hepcidin and alanine transaminase (ALT) (beta = 0.18 ± 0.01, P < 0.0001) was discovered using linear regression in a cohort consisting of 1813 individuals. This association was then validated in the second independent cohort of 1642 individuals (beta = 0.08 ± 0.02, P < 0.0001). Furthermore, consistent with cohort study, by applying both CCl4 and lipopolysaccharide induced mouse liver injury models, at least 2-fold elevations in hepcidin expression, serum ALT and inflammatory cytokine IL-6 were discovered during the initiation stage of liver injury. Our findings suggest that increased serum hepcidin may reflect a protective response to the iron status and elevated serum cytokines during liver injury. Additional studies are warranted to validate these findings and test their potential clinical relevance in patients.
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.|Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.|Department of Nutrition, Research Center for Nutrition and Health, Institute of Nutrition and Food Safety, School of Public Health, School of Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310058, China.
Peng
P
An
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.|Department of Nutrition, Research Center for Nutrition and Health, Institute of Nutrition and Food Safety, School of Public Health, School of Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310058, China.
Hao
H
Wang
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.|Department of Nutrition, Research Center for Nutrition and Health, Institute of Nutrition and Food Safety, School of Public Health, School of Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310058, China.
Qian
Q
Wu
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.|Department of Nutrition, Research Center for Nutrition and Health, Institute of Nutrition and Food Safety, School of Public Health, School of Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310058, China.
Xin
X
Guo
Department of Nutrition, Research Center for Nutrition and Health, Institute of Nutrition and Food Safety, School of Public Health, School of Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310058, China.
Aimin
A
Wu
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200032, P.R. China.
Zhou
Z
Zhang
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200032, P.R. China.
Di
D
Zhang
Department of Nutrition, Research Center for Nutrition and Health, Institute of Nutrition and Food Safety, School of Public Health, School of Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310058, China.
Xiaochen
X
Xu
Department of Nutrition, Research Center for Nutrition and Health, Institute of Nutrition and Food Safety, School of Public Health, School of Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310058, China.
Qianyun
Q
Mao
Department of Nutrition, Research Center for Nutrition and Health, Institute of Nutrition and Food Safety, School of Public Health, School of Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310058, China.
Xiaoyun
X
Shen
Department of Nutrition, Research Center for Nutrition and Health, Institute of Nutrition and Food Safety, School of Public Health, School of Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310058, China.
Lihong
L
Zhang
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
Zhiqi
Z
Xiong
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200032, P.R. China.|Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
Lin
L
He
Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.|Key Laboratory of Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, P.R. China.
Yun
Y
Liu
The first affiliated Hospital, Institute for Translational Medicine, School of Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310058, China.
Junxia
J
Min
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200032, P.R. China.
Daizhan
D
Zhou
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.|Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.|Department of Nutrition, Research Center for Nutrition and Health, Institute of Nutrition and Food Safety, School of Public Health, School of Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310058, China.|Department of Nutrition, Research Center for Nutrition and Health, College of Public Health, Zhengzhou University, Zhengzhou 450001, China.
Fudi
F
Wang
D000410:Alanine Transaminase / Q000097:blood*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood*; D015331:Cohort Studies; D004195:Disease Models, Animal; D005260:Female; D005293:Ferritins / Q000097:blood*; D064451:Hepcidins / Q000097:blood*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D016014:Linear Models; D008099:Liver / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D012307:Risk Factors
D064451:Hepcidins; D005293:Ferritins; D007501:Iron; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase