Serum LEAP2 Levels Across the Spectrum of Metabolic Dysfunction-Associated Fatty Liver Disease: A Potential Noninvasive Biomarker for Severity Stratification
Xinyang Huang,1,* Zihao Deng,1,* Xiaozhou Li,2 Songxin Yan,3 Kunjiang Zhong,1 Fengning Yuan,4 Ligang Liu,5 Chaolin Deng,6 Tingting Liu,7 Ruizhao Zhao,1 Amin Buhe,2 Tianxiong Li,2 Hao Zhao2 1Capital Medical University, Beijing, People’s Republic of China; 2Surgery Centre of Di...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2025-07-01
|
| Series: | Diabetes, Metabolic Syndrome and Obesity |
| Subjects: | |
| Online Access: | https://www.dovepress.com/serum-leap2-levels-across-the-spectrum-of-metabolic-dysfunction-associ-peer-reviewed-fulltext-article-DMSO |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849421834049552384 |
|---|---|
| author | Huang X Deng Z Li X Yan S Zhong K Yuan F Liu L Deng C Liu T Zhao R Buhe A Li T Zhao H |
| author_facet | Huang X Deng Z Li X Yan S Zhong K Yuan F Liu L Deng C Liu T Zhao R Buhe A Li T Zhao H |
| author_sort | Huang X |
| collection | DOAJ |
| description | Xinyang Huang,1,&ast; Zihao Deng,1,&ast; Xiaozhou Li,2 Songxin Yan,3 Kunjiang Zhong,1 Fengning Yuan,4 Ligang Liu,5 Chaolin Deng,6 Tingting Liu,7 Ruizhao Zhao,1 Amin Buhe,2 Tianxiong Li,2 Hao Zhao2 1Capital Medical University, Beijing, People’s Republic of China; 2Surgery Centre of Diabetes Mellitus, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, People’s Republic of China; 3Department of Clinical Laboratory, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 4Beijing Stomatological Hospital, Capital Medical University, Beijing, People’s Republic of China; 5Institute of Therapeutic Innovations and Outcomes (ITIO), College of Pharmacy, The Ohio State University, Columbus, OH, USA; 6Department of Hepatobiliary Surgery, Peking University People’s Hospital, Beijing, People’s Republic of China; 7Department of Hepatobiliary Surgery, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Zhao, Surgery Centre of Diabetes Mellitus, Capital Medical University Affiliated Beijing Shijitan Hospital, Haidian District, 10th Tieyi Road, Beijing, 100038, People’s Republic of China, Tel +86 010 6392 5772, Email 987622272@qq.com Tianxiong Li, Surgery Centre of Diabetes Mellitus, Capital Medical University Affiliated Beijing Shijitan Hospital, Haidian District, 10th Tieyi Road, Beijing, 100038, People’s Republic of China, Tel +86 010 6392 5772, Email doomart@sina.comPurpose: To evaluate circulating liver-expressed antimicrobial peptide 2 (LEAP2) as a potential noninvasive biomarker for the presence of metabolic dysfunction-associated fatty liver disease (MAFLD) and its progression to metabolic dysfunction-associated steatohepatitis (MASH).Patients and Methods: This prospective observational study enrolled obese patients with MAFLD, categorized into simple steatosis (SS) or MASH based on liver histopathology, along with healthy controls (HC). Serum levels LEAP2 were quantified using enzyme-linked immunosorbent assay (ELISA). Baseline characteristics were compared among groups, followed by univariable and multivariate ordinary logistic regression to identify MAFLD predictors. The diagnostic performance of LEAP2 was evaluated through receiver operating characteristic (ROC) curve analysis. Additionally, Hepatic LEAP2 transcriptomic data from public Gene Expression Omnibus (GEO) datasets (GSE126848, GSE135251) were analyzed for validation.Results: Seventy-four participants (24 HC, 24 SS, 26 MASH) were analyzed. Serum LEAP2 levels significantly and progressively increased with MAFLD severity (median ng/mL: HC 11.54, SS 13.62, MASH 18.34; P< 0.001), correlating positively with disease stage (Spearman’s ρ=0.526, P< 0.001). This pattern was validated using hepatic LEAP2 transcript data from GEO datasets (P< 0.001; Spearman’s ρ=0.317, P< 0.001). Multivariate logistic regression identified serum LEAP2 as an independent factor associated with MAFLD presence (OR=1.14, 95% CI 1.03– 1.26; P=0.014), alongside BMI and ALT, while HDL was protective. ROC analysis demonstrated good diagnostic performance for distinguishing MASH from HC (AUC=0.86) and moderate performance for adjacent stages (HC vs SS, AUC=0.70; SS vs MASH, AUC=0.70).Conclusion: Serum LEAP2 levels progressively increase with MAFLD severity and are independently associated with the disease. LEAP2 demonstrates potential as a noninvasive biomarker for assessing MAFLD severity, particularly in distinguishing MASH from healthy individuals. These findings warrant further investigation into LEAP2’s pathophysiological role and therapeutic potential.Keywords: LEAP2, MAFLD, MASH, hepatic steatosis, biomarker |
| format | Article |
| id | doaj-art-b4f0900fc4fd44eaa25e011f7b0cb604 |
| institution | Kabale University |
| issn | 1178-7007 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Diabetes, Metabolic Syndrome and Obesity |
| spelling | doaj-art-b4f0900fc4fd44eaa25e011f7b0cb6042025-08-20T03:31:21ZengDove Medical PressDiabetes, Metabolic Syndrome and Obesity1178-70072025-07-01Volume 18Issue 124392450105019Serum LEAP2 Levels Across the Spectrum of Metabolic Dysfunction-Associated Fatty Liver Disease: A Potential Noninvasive Biomarker for Severity StratificationHuang XDeng Z0Li X1Yan S2Zhong KYuan F3Liu L4Deng C5Liu T6Zhao RBuhe A7Li T8Zhao H9Cancer CenterSurgery Centre of Diabetes MellitusDepartment of Clinical LaboratoryBeijingInstitute of Therapeutic Innovations and Outcomes (ITIO), College of PharmacyDepartment of Hepatobiliary SurgeryDepartment of Hepatobiliary SurgerySurgery Centre of Diabetes MellitusSurgery Centre of Diabetes MellitusSurgery Centre of Diabetes MellitusXinyang Huang,1,&ast; Zihao Deng,1,&ast; Xiaozhou Li,2 Songxin Yan,3 Kunjiang Zhong,1 Fengning Yuan,4 Ligang Liu,5 Chaolin Deng,6 Tingting Liu,7 Ruizhao Zhao,1 Amin Buhe,2 Tianxiong Li,2 Hao Zhao2 1Capital Medical University, Beijing, People’s Republic of China; 2Surgery Centre of Diabetes Mellitus, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, People’s Republic of China; 3Department of Clinical Laboratory, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 4Beijing Stomatological Hospital, Capital Medical University, Beijing, People’s Republic of China; 5Institute of Therapeutic Innovations and Outcomes (ITIO), College of Pharmacy, The Ohio State University, Columbus, OH, USA; 6Department of Hepatobiliary Surgery, Peking University People’s Hospital, Beijing, People’s Republic of China; 7Department of Hepatobiliary Surgery, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Zhao, Surgery Centre of Diabetes Mellitus, Capital Medical University Affiliated Beijing Shijitan Hospital, Haidian District, 10th Tieyi Road, Beijing, 100038, People’s Republic of China, Tel +86 010 6392 5772, Email 987622272@qq.com Tianxiong Li, Surgery Centre of Diabetes Mellitus, Capital Medical University Affiliated Beijing Shijitan Hospital, Haidian District, 10th Tieyi Road, Beijing, 100038, People’s Republic of China, Tel +86 010 6392 5772, Email doomart@sina.comPurpose: To evaluate circulating liver-expressed antimicrobial peptide 2 (LEAP2) as a potential noninvasive biomarker for the presence of metabolic dysfunction-associated fatty liver disease (MAFLD) and its progression to metabolic dysfunction-associated steatohepatitis (MASH).Patients and Methods: This prospective observational study enrolled obese patients with MAFLD, categorized into simple steatosis (SS) or MASH based on liver histopathology, along with healthy controls (HC). Serum levels LEAP2 were quantified using enzyme-linked immunosorbent assay (ELISA). Baseline characteristics were compared among groups, followed by univariable and multivariate ordinary logistic regression to identify MAFLD predictors. The diagnostic performance of LEAP2 was evaluated through receiver operating characteristic (ROC) curve analysis. Additionally, Hepatic LEAP2 transcriptomic data from public Gene Expression Omnibus (GEO) datasets (GSE126848, GSE135251) were analyzed for validation.Results: Seventy-four participants (24 HC, 24 SS, 26 MASH) were analyzed. Serum LEAP2 levels significantly and progressively increased with MAFLD severity (median ng/mL: HC 11.54, SS 13.62, MASH 18.34; P< 0.001), correlating positively with disease stage (Spearman’s ρ=0.526, P< 0.001). This pattern was validated using hepatic LEAP2 transcript data from GEO datasets (P< 0.001; Spearman’s ρ=0.317, P< 0.001). Multivariate logistic regression identified serum LEAP2 as an independent factor associated with MAFLD presence (OR=1.14, 95% CI 1.03– 1.26; P=0.014), alongside BMI and ALT, while HDL was protective. ROC analysis demonstrated good diagnostic performance for distinguishing MASH from HC (AUC=0.86) and moderate performance for adjacent stages (HC vs SS, AUC=0.70; SS vs MASH, AUC=0.70).Conclusion: Serum LEAP2 levels progressively increase with MAFLD severity and are independently associated with the disease. LEAP2 demonstrates potential as a noninvasive biomarker for assessing MAFLD severity, particularly in distinguishing MASH from healthy individuals. These findings warrant further investigation into LEAP2’s pathophysiological role and therapeutic potential.Keywords: LEAP2, MAFLD, MASH, hepatic steatosis, biomarkerhttps://www.dovepress.com/serum-leap2-levels-across-the-spectrum-of-metabolic-dysfunction-associ-peer-reviewed-fulltext-article-DMSOLEAP2MAFLDMASHhepatic steatosisbiomarker |
| spellingShingle | Huang X Deng Z Li X Yan S Zhong K Yuan F Liu L Deng C Liu T Zhao R Buhe A Li T Zhao H Serum LEAP2 Levels Across the Spectrum of Metabolic Dysfunction-Associated Fatty Liver Disease: A Potential Noninvasive Biomarker for Severity Stratification Diabetes, Metabolic Syndrome and Obesity LEAP2 MAFLD MASH hepatic steatosis biomarker |
| title | Serum LEAP2 Levels Across the Spectrum of Metabolic Dysfunction-Associated Fatty Liver Disease: A Potential Noninvasive Biomarker for Severity Stratification |
| title_full | Serum LEAP2 Levels Across the Spectrum of Metabolic Dysfunction-Associated Fatty Liver Disease: A Potential Noninvasive Biomarker for Severity Stratification |
| title_fullStr | Serum LEAP2 Levels Across the Spectrum of Metabolic Dysfunction-Associated Fatty Liver Disease: A Potential Noninvasive Biomarker for Severity Stratification |
| title_full_unstemmed | Serum LEAP2 Levels Across the Spectrum of Metabolic Dysfunction-Associated Fatty Liver Disease: A Potential Noninvasive Biomarker for Severity Stratification |
| title_short | Serum LEAP2 Levels Across the Spectrum of Metabolic Dysfunction-Associated Fatty Liver Disease: A Potential Noninvasive Biomarker for Severity Stratification |
| title_sort | serum leap2 levels across the spectrum of metabolic dysfunction associated fatty liver disease a potential noninvasive biomarker for severity stratification |
| topic | LEAP2 MAFLD MASH hepatic steatosis biomarker |
| url | https://www.dovepress.com/serum-leap2-levels-across-the-spectrum-of-metabolic-dysfunction-associ-peer-reviewed-fulltext-article-DMSO |
| work_keys_str_mv | AT huangx serumleap2levelsacrossthespectrumofmetabolicdysfunctionassociatedfattyliverdiseaseapotentialnoninvasivebiomarkerforseveritystratification AT dengz serumleap2levelsacrossthespectrumofmetabolicdysfunctionassociatedfattyliverdiseaseapotentialnoninvasivebiomarkerforseveritystratification AT lix serumleap2levelsacrossthespectrumofmetabolicdysfunctionassociatedfattyliverdiseaseapotentialnoninvasivebiomarkerforseveritystratification AT yans serumleap2levelsacrossthespectrumofmetabolicdysfunctionassociatedfattyliverdiseaseapotentialnoninvasivebiomarkerforseveritystratification AT zhongk serumleap2levelsacrossthespectrumofmetabolicdysfunctionassociatedfattyliverdiseaseapotentialnoninvasivebiomarkerforseveritystratification AT yuanf serumleap2levelsacrossthespectrumofmetabolicdysfunctionassociatedfattyliverdiseaseapotentialnoninvasivebiomarkerforseveritystratification AT liul serumleap2levelsacrossthespectrumofmetabolicdysfunctionassociatedfattyliverdiseaseapotentialnoninvasivebiomarkerforseveritystratification AT dengc serumleap2levelsacrossthespectrumofmetabolicdysfunctionassociatedfattyliverdiseaseapotentialnoninvasivebiomarkerforseveritystratification AT liut serumleap2levelsacrossthespectrumofmetabolicdysfunctionassociatedfattyliverdiseaseapotentialnoninvasivebiomarkerforseveritystratification AT zhaor serumleap2levelsacrossthespectrumofmetabolicdysfunctionassociatedfattyliverdiseaseapotentialnoninvasivebiomarkerforseveritystratification AT buhea serumleap2levelsacrossthespectrumofmetabolicdysfunctionassociatedfattyliverdiseaseapotentialnoninvasivebiomarkerforseveritystratification AT lit serumleap2levelsacrossthespectrumofmetabolicdysfunctionassociatedfattyliverdiseaseapotentialnoninvasivebiomarkerforseveritystratification AT zhaoh serumleap2levelsacrossthespectrumofmetabolicdysfunctionassociatedfattyliverdiseaseapotentialnoninvasivebiomarkerforseveritystratification |