Pemafibrate Ameliorates Steatotic Liver Disease Regardless of Endothelial Dysfunction in Mice
Abstract
1. Introduction
2. Materials and Methods
2.1. Animal Preparation
2.2. Plasma Biochemical Analysis
2.3. Measurements of Hepatic Lipid Contents
2.4. Histopathological Examination of Liver Tissues
2.5. Immunohistochemistry of Liver Tissues
2.6. In Situ Superoxide Detection of Liver Tissues
2.7. Gene Expression Analysis of Liver Tissues
2.8. Western Blot Analysis of Liver Tissues
2.9. Statistical Analysis
3. Results
3.1. Body Weight, Liver Weight and Biochemical Analysis
3.2. Pemafibrate Ameliorates Steatotic Lesions and Attenuates Macrophage Infiltration in the Liver Regardless of eNOS
3.3. Pemafibrate Attenuates Hepatic Production of Reactive Oxygen Species Regardless of eNOS
3.4. Quantitative PCR Analysis of MASLD-Associated Genes in the Liver
3.4.1. Pemafibrate Attenuates Expression of NADPH Oxidase Subunit Genes Regardless of eNOS
3.4.2. Pemafibrate Attenuates Expression of M1 Macrophages and Macrophage-Associated Genes Regardless of eNOS
3.4.3. Pemafibrate Attenuates Expression of Inflammatory Cytokine, Chemokine and Profibrotic Genes Regardless of eNOS
3.4.4. Other Candidate Genes
3.4.5. Analysis of Gene Expression Clustergrams and Volcano Plots Shows Comprehensive Anti-MASLD Effects of Pemafibrate Regardless of eNOS
3.5. Pemafibrate Activates Hepatic AMPKα and Attenuates 4-HNE Regardless of eNOS
4. Discussion
4.1. Pemafibrate Attenuates Hepatic Oxidative Stress Regardless of eNOS
4.2. Pemafibrate Attenuates Hepatic Inflammatory Cytokines and Chemokines Regardless of eNOS
4.3. Pemafibrate Activates Hepatic AMPK Regardless of eNOS
4.4. Unresolved Issues
4.5. Experimental Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
MASLD | Metabolic-Dysfunction-Associated Steatotic Liver Disease |
eNOS | Endothelial Nitric Oxide Synthase |
PPARα | Peroxisome-Proliferator-Activated Receptor α |
NADPH | Nicotinamide Adenine Dinucleotide Phosphate |
ROS | Reactive Oxygen Species |
DHE | Dihydroethidium |
References
- Wong, V.W.; Ekstedt, M.; Wong, G.L.; Hagstrom, H. Changing epidemiology, global trends and implications for outcomes of NAFLD. J. Hepatol. 2023, 79, 842–852. [Google Scholar] [CrossRef] [PubMed]
- Gambino, R.; Musso, G.; Cassader, M. Redox balance in the pathogenesis of nonalcoholic fatty liver disease: Mechanisms and therapeutic opportunities. Antioxid. Redox Signal. 2011, 15, 1325–1365. [Google Scholar] [CrossRef] [PubMed]
- Younossi, Z.M.; Kalligeros, M.; Henry, L. Epidemiology of metabolic dysfunction-associated steatotic liver disease. Clin. Mol. Hepatol. 2025, 31, S32–S50. [Google Scholar] [CrossRef] [PubMed]
- Adams, L.A.; Anstee, Q.M.; Tilg, H.; Targher, G. Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases. Gut 2017, 66, 1138–1153. [Google Scholar] [CrossRef] [PubMed]
- Angulo, P.; Kleiner, D.E.; Dam-Larsen, S.; Adams, L.A.; Bjornsson, E.S.; Charatcharoenwitthaya, P.; Mills, P.R.; Keach, J.C.; Lafferty, H.D.; Stahler, A.; et al. Liver Fibrosis, but No Other Histologic Features, Is Associated with Long-term Outcomes of Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology 2015, 149, 389–397.e10. [Google Scholar] [CrossRef] [PubMed]
- Nozaki, Y.; Fujita, K.; Wada, K.; Yoneda, M.; Shinohara, Y.; Imajo, K.; Ogawa, Y.; Kessoku, T.; Nakamuta, M.; Saito, S.; et al. Deficiency of eNOS exacerbates early-stage NAFLD pathogenesis by changing the fat distribution. BMC Gastroenterol. 2015, 15, 177. [Google Scholar] [CrossRef] [PubMed]
- Cunningham, R.P.; Moore, M.P.; Dashek, R.J.; Meers, G.M.; Takahashi, T.; Sheldon, R.D.; Wheeler, A.A.; Diaz-Arias, A.; Ibdah, J.A.; Parks, E.J.; et al. Critical Role for Hepatocyte-Specific eNOS in NAFLD and NASH. Diabetes 2021, 70, 2476–2491. [Google Scholar] [CrossRef] [PubMed]
- Persico, M.; Masarone, M.; Damato, A.; Ambrosio, M.; Federico, A.; Rosato, V.; Bucci, T.; Carrizzo, A.; Vecchione, C. Non alcoholic fatty liver disease and eNOS dysfunction in humans. BMC Gastroenterol. 2017, 17, 35. [Google Scholar] [CrossRef] [PubMed]
- Madrazo, J.A.; Kelly, D.P. The PPAR trio: Regulators of myocardial energy metabolism in health and disease. J. Mol. Cell. Cardiol. 2008, 44, 968–975. [Google Scholar] [CrossRef] [PubMed]
- Braissant, O.; Foufelle, F.; Scotto, C.; Dauca, M.; Wahli, W. Differential expression of peroxisome proliferator-activated receptors (PPARs): Tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat. Endocrinology 1996, 137, 354–366. [Google Scholar] [CrossRef] [PubMed]
- Montaigne, D.; Butruille, L.; Staels, B. PPAR control of metabolism and cardiovascular functions. Nat. Rev. Cardiol. 2021, 18, 809–823. [Google Scholar] [CrossRef] [PubMed]
- Hu, S.; Wang, Z.; Zhu, K.; Shi, H.; Qin, F.; Zhang, T.; Tian, S.; Ji, Y.; Zhang, J.; Qin, J.; et al. USP29 alleviates the progression of MASLD by stabilizing ACSL5 through K48 deubiquitination. Clin. Mol. Hepatol. 2025, 31, 147–165. [Google Scholar] [CrossRef] [PubMed]
- Yamashita, S.; Masuda, D.; Matsuzawa, Y. Pemafibrate, a New Selective PPARalpha Modulator: Drug Concept and Its Clinical Applications for Dyslipidemia and Metabolic Diseases. Curr. Atheroscler. Rep. 2020, 22, 5. [Google Scholar] [CrossRef] [PubMed]
- Iwasa, M.; Sugimoto, R.; Eguchi, A.; Tamai, Y.; Shigefuku, R.; Fujiwara, N.; Tanaka, H.; Kobayashi, Y.; Ikoma, J.; Kaito, M.; et al. Effectiveness of 1-year pemafibrate treatment on steatotic liver disease: The influence of alcohol consumption. Eur. J. Gastroenterol. Hepatol. 2024, 36, 793–801. [Google Scholar] [CrossRef] [PubMed]
- Sumida, Y.; Toyoda, H.; Yasuda, S.; Kimoto, S.; Sakamoto, K.; Nakade, Y.; Ito, K.; Osonoi, T.; Yoneda, M. Comparison of Efficacy between Pemafibrate and Omega-3-Acid Ethyl Ester in the Liver: The PORTRAIT Study. J. Atheroscler. Thromb. 2024, 31, 1620–1633. [Google Scholar] [CrossRef] [PubMed]
- Ichikawa, T.; Oba, H.; Owada, M.; Watanabe, K.; Yoshimura, T.; Fuchigami, A.; Nakamura, A. Evaluation of the effects of pemafibrate on metabolic dysfunction-associated steatotic liver disease with hypertriglyceridemia using magnetic resonance elastography combined with fibrosis-4 index and the magnetic resonance imaging-aspartate aminotransferase score. JGH Open 2023, 7, 959–965. [Google Scholar] [CrossRef] [PubMed]
- Bentanachs, R.; Miro, L.; Sanchez, R.M.; Ramirez-Carrasco, P.; Amat, C.; Alegret, M.; Perez, A.; Roglans, N.; Laguna, J.C. Pemafibrate abrogates SLD in a rat experimental dietary model, inducing a shift in fecal bile acids and microbiota composition. Biomed. Pharmacother. 2024, 177, 117067. [Google Scholar] [CrossRef] [PubMed]
- Sasaki, Y.; Asahiyama, M.; Tanaka, T.; Yamamoto, S.; Murakami, K.; Kamiya, W.; Matsumura, Y.; Osawa, T.; Anai, M.; Fruchart, J.C.; et al. Pemafibrate, a selective PPARalpha modulator, prevents non-alcoholic steatohepatitis development without reducing the hepatic triglyceride content. Sci. Rep. 2020, 10, 7818. [Google Scholar] [CrossRef] [PubMed]
- Sasaki, Y.; Raza-Iqbal, S.; Tanaka, T.; Murakami, K.; Anai, M.; Osawa, T.; Matsumura, Y.; Sakai, J.; Kodama, T. Gene Expression Profiles Induced by a Novel Selective Peroxisome Proliferator-Activated Receptor alpha Modulator (SPPARMalpha) Pemafibrate. Int. J. Mol. Sci. 2019, 20, 5682. [Google Scholar] [CrossRef] [PubMed]
- Suto, K.; Fukuda, D.; Shinohara, M.; Ganbaatar, B.; Yagi, S.; Kusunose, K.; Yamada, H.; Soeki, T.; Hirata, K.I.; Sata, M. Pemafibrate, A Novel Selective Peroxisome Proliferator-Activated Receptor alpha Modulator, Reduces Plasma Eicosanoid Levels and Ameliorates Endothelial Dysfunction in Diabetic Mice. J. Atheroscler. Thromb. 2021, 28, 1349–1360. [Google Scholar] [CrossRef] [PubMed]
- Kawanishi, H.; Ohashi, K.; Ogawa, H.; Otaka, N.; Takikawa, T.; Fang, L.; Ozaki, Y.; Takefuji, M.; Murohara, T.; Ouchi, N. A novel selective PPARalpha modulator, pemafibrate promotes ischemia-induced revascularization through the eNOS-dependent mechanisms. PLoS ONE 2020, 15, e0235362. [Google Scholar] [CrossRef] [PubMed]
- Ichimura-Shimizu, M.; Omagari, K.; Yamashita, M.; Tsuneyama, K. Development of a novel mouse model of diet-induced nonalcoholic steatohepatitis-related progressive bridging fibrosis. Biosci. Biotechnol. Biochem. 2021, 85, 941–947. [Google Scholar] [CrossRef] [PubMed]
- Ichimura-Shimizu, M.; Tsuchiyama, Y.; Morimoto, Y.; Matsumoto, M.; Kobayashi, T.; Sumida, S.; Kakimoto, T.; Oya, T.; Ogawa, H.; Yamashita, M.; et al. A Novel Mouse Model of Nonalcoholic Steatohepatitis Suggests that Liver Fibrosis Initiates around Lipid-Laden Macrophages. Am. J. Pathol. 2022, 192, 31–42. [Google Scholar] [CrossRef] [PubMed]
- Kleiner, D.E.; Brunt, E.M.; Van Natta, M.; Behling, C.; Contos, M.J.; Cummings, O.W.; Ferrell, L.D.; Liu, Y.C.; Torbenson, M.S.; Unalp-Arida, A.; et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005, 41, 1313–1321. [Google Scholar] [CrossRef] [PubMed]
- Kurahashi, K.; Inoue, S.; Yoshida, S.; Ikeda, Y.; Morimoto, K.; Uemoto, R.; Ishikawa, K.; Kondo, T.; Yuasa, T.; Endo, I.; et al. The Role of Heparin Cofactor II in the Regulation of Insulin Sensitivity and Maintenance of Glucose Homeostasis in Humans and Mice. J. Atheroscler. Thromb. 2017, 24, 1215–1230. [Google Scholar] [CrossRef] [PubMed]
- Ikeda, Y.; Watanabe, H.; Shiuchi, T.; Hamano, H.; Horinouchi, Y.; Imanishi, M.; Goda, M.; Zamami, Y.; Takechi, K.; Izawa-Ishizawa, Y.; et al. Deletion of H-ferritin in macrophages alleviates obesity and diabetes induced by high-fat diet in mice. Diabetologia 2020, 63, 1588–1602. [Google Scholar] [CrossRef] [PubMed]
- Mladenic, K.; Lenartic, M.; Marinovic, S.; Polic, B.; Wensveen, F.M. The "Domino effect" in MASLD: The inflammatory cascade of steatohepatitis. Eur. J. Immunol. 2024, 54, e2149641. [Google Scholar] [CrossRef] [PubMed]
- Tamilmani, P.; Sathibabu Uddandrao, V.V.; Chandrasekaran, P.; Saravanan, G.; Brahma Naidu, P.; Sengottuvelu, S.; Vadivukkarasi, S. Linalool attenuates lipid accumulation and oxidative stress in metabolic dysfunction-associated steatotic liver disease via Sirt1/Akt/PPRA-alpha/AMPK and Nrf-2/HO-1 signaling pathways. Clin. Res. Hepatol. Gastroenterol. 2023, 47, 102231. [Google Scholar] [CrossRef] [PubMed]
- Hardwick, R.N.; Fisher, C.D.; Canet, M.J.; Lake, A.D.; Cherrington, N.J. Diversity in antioxidant response enzymes in progressive stages of human nonalcoholic fatty liver disease. Drug Metab. Dispos. 2010, 38, 2293–2301. [Google Scholar] [CrossRef] [PubMed]
- Choi, Y.; Abdelmegeed, M.A.; Song, B.J. Diet high in fructose promotes liver steatosis and hepatocyte apoptosis in C57BL/6J female mice: Role of disturbed lipid homeostasis and increased oxidative stress. Food Chem. Toxicol. 2017, 103, 111–121. [Google Scholar] [CrossRef] [PubMed]
- Maki, T.; Maeda, Y.; Sonoda, N.; Makimura, H.; Kimura, S.; Maeno, S.; Takayanagi, R.; Inoguchi, T. Renoprotective effect of a novel selective PPARalpha modulator K-877 in db/db mice: A role of diacylglycerol-protein kinase C-NAD(P)H oxidase pathway. Metabolism 2017, 71, 33–45. [Google Scholar] [CrossRef] [PubMed]
- Li, W.; Xu, J.; Guo, X.; Xia, X.; Sun, Y. Pemafibrate suppresses oxidative stress and apoptosis under cardiomyocyte ischemia-reperfusion injury in type 1 diabetes mellitus. Exp. Ther. Med. 2021, 21, 331. [Google Scholar] [CrossRef] [PubMed]
- Anegawa, T.; Sasaki, K.I.; Ishizaki, Y.; Negoto, S.; Oryoji, A.; Nakamura, E.; Otsuka, H.; Hiromatsu, S.; Fukumoto, Y.; Tayama, E. Effects of Pemafibrate on Reducing Oxidative Stress and Augmenting Angiogenesis in Ischemic Limb Tissue. Kurume Med. J. 2024, 69, 167–174. [Google Scholar] [CrossRef] [PubMed]
- Newaz, M.; Blanton, A.; Fidelis, P.; Oyekan, A. NAD(P)H oxidase/nitric oxide interactions in peroxisome proliferator activated receptor (PPAR)alpha-mediated cardiovascular effects. Mutat. Res. 2005, 579, 163–171. [Google Scholar] [CrossRef] [PubMed]
- Matsushima, S.; Kuroda, J.; Ago, T.; Zhai, P.; Ikeda, Y.; Oka, S.; Fong, G.H.; Tian, R.; Sadoshima, J. Broad suppression of NADPH oxidase activity exacerbates ischemia/reperfusion injury through inadvertent downregulation of hypoxia-inducible factor-1alpha and upregulation of peroxisome proliferator-activated receptor-alpha. Circ. Res. 2013, 112, 1135–1149. [Google Scholar] [CrossRef] [PubMed]
- Gadd, V.L.; Skoien, R.; Powell, E.E.; Fagan, K.J.; Winterford, C.; Horsfall, L.; Irvine, K.; Clouston, A.D. The portal inflammatory infiltrate and ductular reaction in human nonalcoholic fatty liver disease. Hepatology 2014, 59, 1393–1405. [Google Scholar] [CrossRef] [PubMed]
- De Ponti, F.F.; Liu, Z.; Scott, C.L. Understanding the complex macrophage landscape in MASLD. JHEP Rep. 2024, 6, 101196. [Google Scholar] [CrossRef] [PubMed]
- Kazankov, K.; Jorgensen, S.M.D.; Thomsen, K.L.; Moller, H.J.; Vilstrup, H.; George, J.; Schuppan, D.; Gronbaek, H. The role of macrophages in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Nat. Rev. Gastroenterol. Hepatol. 2019, 16, 145–159. [Google Scholar] [CrossRef] [PubMed]
- Matsuda, M.; Seki, E. Hepatic Stellate Cell-Macrophage Crosstalk in Liver Fibrosis and Carcinogenesis. Semin. Liver Dis. 2020, 40, 307–320. [Google Scholar] [CrossRef] [PubMed]
- Vonderlin, J.; Chavakis, T.; Sieweke, M.; Tacke, F. The Multifaceted Roles of Macrophages in NAFLD Pathogenesis. Cell. Mol. Gastroenterol. Hepatol. 2023, 15, 1311–1324. [Google Scholar] [CrossRef] [PubMed]
- Zhang, T.; Hu, J.; Wang, X.; Zhao, X.; Li, Z.; Niu, J.; Steer, C.J.; Zheng, G.; Song, G. MicroRNA-378 promotes hepatic inflammation and fibrosis via modulation of the NF-kappaB-TNFalpha pathway. J. Hepatol. 2019, 70, 87–96. [Google Scholar] [CrossRef] [PubMed]
- Hall, K.C.; Bernier, S.G.; Jacobson, S.; Liu, G.; Zhang, P.Y.; Sarno, R.; Catanzano, V.; Currie, M.G.; Masferrer, J.L. sGC stimulator praliciguat suppresses stellate cell fibrotic transformation and inhibits fibrosis and inflammation in models of NASH. Proc. Natl. Acad. Sci. USA 2019, 116, 11057–11062. [Google Scholar] [CrossRef] [PubMed]
- Zhao, P.; Sun, X.; Chaggan, C.; Liao, Z.; In Wong, K.; He, F.; Singh, S.; Loomba, R.; Karin, M.; Witztum, J.L.; et al. An AMPK-caspase-6 axis controls liver damage in nonalcoholic steatohepatitis. Science 2020, 367, 652–660. [Google Scholar] [CrossRef] [PubMed]
- Feng, J.; Li, M.H.; Yao, T.T.; Yi, X.J.; Gao, H.N. Research progress on AMPK in the pathogenesis and treatment of MASLD. Front. Immunol. 2025, 16, 1558041. [Google Scholar] [CrossRef] [PubMed]
- Ratman, D.; Mylka, V.; Bougarne, N.; Pawlak, M.; Caron, S.; Hennuyer, N.; Paumelle, R.; De Cauwer, L.; Thommis, J.; Rider, M.H.; et al. Chromatin recruitment of activated AMPK drives fasting response genes co-controlled by GR and PPARalpha. Nucleic Acids Res. 2016, 44, 10539–10553. [Google Scholar] [CrossRef] [PubMed]
- Gao, Y.; Zhou, Q.; Wang, H.; Xin, G.; Wang, T.; Zhang, K.; Yu, X.; Wen, A.; Wu, Q.; Li, X.; et al. Isoxanthohumol improves hepatic lipid metabolism via regulating the AMPK/PPARalpha and PI3K/AKT signaling pathways in hyperlipidemic mice. Food Sci. Nutr. 2024, 12, 8846–8857. [Google Scholar] [CrossRef] [PubMed]
- Yagi, S.; Aihara, K.; Ikeda, Y.; Sumitomo, Y.; Yoshida, S.; Ise, T.; Iwase, T.; Ishikawa, K.; Azuma, H.; Akaike, M.; et al. Pitavastatin, an HMG-CoA reductase inhibitor, exerts eNOS-independent protective actions against angiotensin II induced cardiovascular remodeling and renal insufficiency. Circ. Res. 2008, 102, 68–76. [Google Scholar] [CrossRef] [PubMed]
- Yagi, S.; Akaike, M.; Aihara, K.; Ishikawa, K.; Iwase, T.; Ikeda, Y.; Soeki, T.; Yoshida, S.; Sumitomo-Ueda, Y.; Matsumoto, T.; et al. Endothelial nitric oxide synthase-independent protective action of statin against angiotensin II-induced atrial remodeling via reduced oxidant injury. Hypertension 2010, 55, 918–923. [Google Scholar] [CrossRef] [PubMed]
- Mitsuhashi, T.; Uemoto, R.; Ishikawa, K.; Yoshida, S.; Ikeda, Y.; Yagi, S.; Matsumoto, T.; Akaike, M.; Aihara, K.I. Endothelial Nitric Oxide Synthase-Independent Pleiotropic Effects of Pitavastatin Against Atherogenesis and Limb Ischemia in Mice. J. Atheroscler. Thromb. 2018, 25, 65–80. [Google Scholar] [CrossRef] [PubMed]
- Cui, X.S.; Li, H.Z.; Li, L.; Xie, C.Z.; Gao, J.M.; Chen, Y.Y.; Zhang, H.Y.; Hao, W.; Fu, J.H.; Guo, H. Rodent model of metabolic dysfunction-associated fatty liver disease: A systematic review. J. Gastroenterol. Hepatol. 2025, 40, 48–66. [Google Scholar] [CrossRef] [PubMed]
- Vacca, M.; Kamzolas, I.; Harder, L.M.; Oakley, F.; Trautwein, C.; Hatting, M.; Ross, T.; Bernardo, B.; Oldenburger, A.; Hjuler, S.T.; et al. An unbiased ranking of murine dietary models based on their proximity to human metabolic dysfunction-associated steatotic liver disease (MASLD). Nat. Metab. 2024, 6, 1178–1196. [Google Scholar] [CrossRef] [PubMed]
- Ichimura, M.; Kawase, M.; Masuzumi, M.; Sakaki, M.; Nagata, Y.; Tanaka, K.; Suruga, K.; Tamaru, S.; Kato, S.; Tsuneyama, K.; et al. High-fat and high-cholesterol diet rapidly induces non-alcoholic steatohepatitis with advanced fibrosis in Sprague-Dawley rats. Hepatol. Res. 2015, 45, 458–469. [Google Scholar] [CrossRef] [PubMed]
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Hara, T.; Yamagami, H.; Uemoto, R.; Sekine, A.; Kaneko, Y.; Miyataka, K.; Hori, T.; Ichimura-Shimizu, M.; Funamoto, M.; Harada, T.; et al. Pemafibrate Ameliorates Steatotic Liver Disease Regardless of Endothelial Dysfunction in Mice. Antioxidants 2025, 14, 891. https://doi.org/10.3390/antiox14070891
Hara T, Yamagami H, Uemoto R, Sekine A, Kaneko Y, Miyataka K, Hori T, Ichimura-Shimizu M, Funamoto M, Harada T, et al. Pemafibrate Ameliorates Steatotic Liver Disease Regardless of Endothelial Dysfunction in Mice. Antioxidants. 2025; 14(7):891. https://doi.org/10.3390/antiox14070891
Chicago/Turabian StyleHara, Tomoyo, Hiroki Yamagami, Ryoko Uemoto, Akiko Sekine, Yousuke Kaneko, Kohsuke Miyataka, Taiki Hori, Mayuko Ichimura-Shimizu, Masafumi Funamoto, Takeshi Harada, and et al. 2025. "Pemafibrate Ameliorates Steatotic Liver Disease Regardless of Endothelial Dysfunction in Mice" Antioxidants 14, no. 7: 891. https://doi.org/10.3390/antiox14070891
APA StyleHara, T., Yamagami, H., Uemoto, R., Sekine, A., Kaneko, Y., Miyataka, K., Hori, T., Ichimura-Shimizu, M., Funamoto, M., Harada, T., Yuasa, T., Nakamura, S., Endo, I., Matsuoka, K.-i., Kawano, Y., Tsuneyama, K., Ikeda, Y., & Aihara, K.-i. (2025). Pemafibrate Ameliorates Steatotic Liver Disease Regardless of Endothelial Dysfunction in Mice. Antioxidants, 14(7), 891. https://doi.org/10.3390/antiox14070891