Semaglutide reduces tumor burden in the GAN diet-induced obese and biopsy-confirmed mouse model of NASH-HCC with advanced fibrosis

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Semaglutide reduces tumor burden in the GAN diet-induced obese and biopsy-confirmed mouse model of NASH-HCC with advanced fibrosis. / Hansen, Henrik H; Pors, Susanne; Andersen, Maja W; Vyberg, Mogens; Nøhr-Meldgaard, Jacob; Nielsen, Malte Hasle; Oró, Denise; Madsen, Martin Rønn; Lewinska, Monika; Møllerhøj, Mathias B; Madsen, Andreas Nygaard; Feigh, Michael.

In: Scientific Reports, Vol. 13, No. 1, 23056, 2023.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Hansen, HH, Pors, S, Andersen, MW, Vyberg, M, Nøhr-Meldgaard, J, Nielsen, MH, Oró, D, Madsen, MR, Lewinska, M, Møllerhøj, MB, Madsen, AN & Feigh, M 2023, 'Semaglutide reduces tumor burden in the GAN diet-induced obese and biopsy-confirmed mouse model of NASH-HCC with advanced fibrosis', Scientific Reports, vol. 13, no. 1, 23056. https://doi.org/10.1038/s41598-023-50328-5

APA

Hansen, H. H., Pors, S., Andersen, M. W., Vyberg, M., Nøhr-Meldgaard, J., Nielsen, M. H., Oró, D., Madsen, M. R., Lewinska, M., Møllerhøj, M. B., Madsen, A. N., & Feigh, M. (2023). Semaglutide reduces tumor burden in the GAN diet-induced obese and biopsy-confirmed mouse model of NASH-HCC with advanced fibrosis. Scientific Reports, 13(1), [23056]. https://doi.org/10.1038/s41598-023-50328-5

Vancouver

Hansen HH, Pors S, Andersen MW, Vyberg M, Nøhr-Meldgaard J, Nielsen MH et al. Semaglutide reduces tumor burden in the GAN diet-induced obese and biopsy-confirmed mouse model of NASH-HCC with advanced fibrosis. Scientific Reports. 2023;13(1). 23056. https://doi.org/10.1038/s41598-023-50328-5

Author

Hansen, Henrik H ; Pors, Susanne ; Andersen, Maja W ; Vyberg, Mogens ; Nøhr-Meldgaard, Jacob ; Nielsen, Malte Hasle ; Oró, Denise ; Madsen, Martin Rønn ; Lewinska, Monika ; Møllerhøj, Mathias B ; Madsen, Andreas Nygaard ; Feigh, Michael. / Semaglutide reduces tumor burden in the GAN diet-induced obese and biopsy-confirmed mouse model of NASH-HCC with advanced fibrosis. In: Scientific Reports. 2023 ; Vol. 13, No. 1.

Bibtex

@article{1a8827a9533546d29bb1416e7d939637,

title = "Semaglutide reduces tumor burden in the GAN diet-induced obese and biopsy-confirmed mouse model of NASH-HCC with advanced fibrosis",

abstract = "Non-alcoholic steatohepatitis (NASH) is emerging as a major cause of hepatocellular carcinoma (HCC), however, it is not resolved if compounds in late-stage clinical development for NASH may have additional therapeutic benefits in NASH-driven HCC (NASH-HCC). Here, we profiled monotherapy with semaglutide (glucagon-like-receptor-1 receptor agonist) and lanifibranor (pan-peroxisome proliferator-activated receptor agonist) in a diet-induced obese (DIO) mouse model of NASH-HCC. Disease progression was characterized in male C57BL/6 J mice fed the GAN (Gubra Amylin NASH) diet high in fat, fructose and cholesterol for 12-72 weeks (n = 15 per group). Other GAN DIO-NASH-HCC mice fed the GAN diet for 54 weeks and with biopsy-confirmed NASH (NAFLD Activity Score ≥ 5) and advanced fibrosis (stage F3) received vehicle (n = 16), semaglutide (30 nmol/kg, s.c., n = 15), or lanifibranor (30 mg/kg, p.o., n = 15) once daily for 14 weeks. GAN DIO-NASH-HCC mice demonstrated progressive NASH, fibrosis and HCC burden. Tumors presented with histological and molecular signatures of poor prognostic HCC. Consistent with clinical trial outcomes in NASH patients, both lanifibranor and semaglutide improved NASH while only lanifibranor reduced fibrosis in GAN DIO-NASH-HCC mice. Notably, only semaglutide reduced tumor burden in GAN DIO-NASH-HCC mice. In conclusion, the GAN DIO-NASH-HCC mouse is a clinical translational model of NASH-HCC. Semaglutide improves both NASH and tumor burden in GAN DIO-NASH-HCC mice, highlighting the suitability of this preclinical model for profiling novel drug therapies targeting NASH-HCC.",

keywords = "Humans, Mice, Animals, Male, Non-alcoholic Fatty Liver Disease/complications, Carcinoma, Hepatocellular/etiology, Liver/pathology, Tumor Burden, Liver Neoplasms/pathology, Diet, High-Fat/adverse effects, Mice, Inbred C57BL, Obesity/complications, Liver Cirrhosis/pathology, Disease Models, Animal, Biopsy/adverse effects",

author = "Hansen, {Henrik H} and Susanne Pors and Andersen, {Maja W} and Mogens Vyberg and Jacob N{\o}hr-Meldgaard and Nielsen, {Malte Hasle} and Denise Or{\'o} and Madsen, {Martin R{\o}nn} and Monika Lewinska and M{\o}llerh{\o}j, {Mathias B} and Madsen, {Andreas Nygaard} and Michael Feigh",

note = "{\textcopyright} 2023. The Author(s).",

year = "2023",

doi = "10.1038/s41598-023-50328-5",

language = "English",

volume = "13",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "nature publishing group",

number = "1",

}

RIS

TY - JOUR

T1 - Semaglutide reduces tumor burden in the GAN diet-induced obese and biopsy-confirmed mouse model of NASH-HCC with advanced fibrosis

AU - Hansen, Henrik H

AU - Pors, Susanne

AU - Andersen, Maja W

AU - Vyberg, Mogens

AU - Nøhr-Meldgaard, Jacob

AU - Nielsen, Malte Hasle

AU - Oró, Denise

AU - Madsen, Martin Rønn

AU - Lewinska, Monika

AU - Møllerhøj, Mathias B

AU - Madsen, Andreas Nygaard

AU - Feigh, Michael

PY - 2023

Y1 - 2023

N2 - Non-alcoholic steatohepatitis (NASH) is emerging as a major cause of hepatocellular carcinoma (HCC), however, it is not resolved if compounds in late-stage clinical development for NASH may have additional therapeutic benefits in NASH-driven HCC (NASH-HCC). Here, we profiled monotherapy with semaglutide (glucagon-like-receptor-1 receptor agonist) and lanifibranor (pan-peroxisome proliferator-activated receptor agonist) in a diet-induced obese (DIO) mouse model of NASH-HCC. Disease progression was characterized in male C57BL/6 J mice fed the GAN (Gubra Amylin NASH) diet high in fat, fructose and cholesterol for 12-72 weeks (n = 15 per group). Other GAN DIO-NASH-HCC mice fed the GAN diet for 54 weeks and with biopsy-confirmed NASH (NAFLD Activity Score ≥ 5) and advanced fibrosis (stage F3) received vehicle (n = 16), semaglutide (30 nmol/kg, s.c., n = 15), or lanifibranor (30 mg/kg, p.o., n = 15) once daily for 14 weeks. GAN DIO-NASH-HCC mice demonstrated progressive NASH, fibrosis and HCC burden. Tumors presented with histological and molecular signatures of poor prognostic HCC. Consistent with clinical trial outcomes in NASH patients, both lanifibranor and semaglutide improved NASH while only lanifibranor reduced fibrosis in GAN DIO-NASH-HCC mice. Notably, only semaglutide reduced tumor burden in GAN DIO-NASH-HCC mice. In conclusion, the GAN DIO-NASH-HCC mouse is a clinical translational model of NASH-HCC. Semaglutide improves both NASH and tumor burden in GAN DIO-NASH-HCC mice, highlighting the suitability of this preclinical model for profiling novel drug therapies targeting NASH-HCC.

AB - Non-alcoholic steatohepatitis (NASH) is emerging as a major cause of hepatocellular carcinoma (HCC), however, it is not resolved if compounds in late-stage clinical development for NASH may have additional therapeutic benefits in NASH-driven HCC (NASH-HCC). Here, we profiled monotherapy with semaglutide (glucagon-like-receptor-1 receptor agonist) and lanifibranor (pan-peroxisome proliferator-activated receptor agonist) in a diet-induced obese (DIO) mouse model of NASH-HCC. Disease progression was characterized in male C57BL/6 J mice fed the GAN (Gubra Amylin NASH) diet high in fat, fructose and cholesterol for 12-72 weeks (n = 15 per group). Other GAN DIO-NASH-HCC mice fed the GAN diet for 54 weeks and with biopsy-confirmed NASH (NAFLD Activity Score ≥ 5) and advanced fibrosis (stage F3) received vehicle (n = 16), semaglutide (30 nmol/kg, s.c., n = 15), or lanifibranor (30 mg/kg, p.o., n = 15) once daily for 14 weeks. GAN DIO-NASH-HCC mice demonstrated progressive NASH, fibrosis and HCC burden. Tumors presented with histological and molecular signatures of poor prognostic HCC. Consistent with clinical trial outcomes in NASH patients, both lanifibranor and semaglutide improved NASH while only lanifibranor reduced fibrosis in GAN DIO-NASH-HCC mice. Notably, only semaglutide reduced tumor burden in GAN DIO-NASH-HCC mice. In conclusion, the GAN DIO-NASH-HCC mouse is a clinical translational model of NASH-HCC. Semaglutide improves both NASH and tumor burden in GAN DIO-NASH-HCC mice, highlighting the suitability of this preclinical model for profiling novel drug therapies targeting NASH-HCC.

KW - Humans

KW - Mice

KW - Animals

KW - Male

KW - Non-alcoholic Fatty Liver Disease/complications

KW - Carcinoma, Hepatocellular/etiology

KW - Liver/pathology

KW - Tumor Burden

KW - Liver Neoplasms/pathology

KW - Diet, High-Fat/adverse effects

KW - Mice, Inbred C57BL

KW - Obesity/complications

KW - Liver Cirrhosis/pathology

KW - Disease Models, Animal

KW - Biopsy/adverse effects

U2 - 10.1038/s41598-023-50328-5

DO - 10.1038/s41598-023-50328-5

M3 - Journal article

C2 - 38155202

VL - 13

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 23056

ER -

ID: 387699287

Department of Biology