Ma YR, Miao WL, Li N, Zhang GZ, Ren ZG. Dual effects of a high-protein diet on metabolic dysfunction-associated steatotic liver disease: Basic research on precision clinical interventions. World J Gastroenterol 2026; 32(41): 120035 [DOI: 10.3748/wjg.120035]
Corresponding Author of This Article
Zhi-Gang Ren, MD, PhD, Department of Infectious Diseases, State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, No. 46 Jianshe East Road, Zhengzhou 450052, Henan Province, China. fccrenzg@zzu.edu.cn
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Gastroenterology & Hepatology
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review-article
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Ma YR, Miao WL, Li N, Zhang GZ, Ren ZG. Dual effects of a high-protein diet on metabolic dysfunction-associated steatotic liver disease: Basic research on precision clinical interventions. World J Gastroenterol 2026; 32(41): 120035 [DOI: 10.3748/wjg.120035]
World J Gastroenterol. Nov 7, 2026; 32(41): 120035 Published online Nov 7, 2026. doi: 10.3748/wjg.120035
Dual effects of a high-protein diet on metabolic dysfunction-associated steatotic liver disease: Basic research on precision clinical interventions
Ya-Rong Ma, Wen-Long Miao, Na Li, Gui-Zhen Zhang, Zhi-Gang Ren
Ya-Rong Ma, Zhi-Gang Ren, Department of Infectious Diseases, State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, Zhengzhou 450052, Henan Province, China
Wen-Long Miao, Na Li, Gui-Zhen Zhang, Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Co-first authors: Ya-Rong Ma and Wen-Long Miao.
Co-corresponding authors: Gui-Zhen Zhang and Zhi-Gang Ren.
Author contributions: Ma YR and Miao WL contributed to the visualization, formal analysis and wrote the manuscript, and they are designated as co-first authors. Li N contributed to the figure preparation and revised the manuscript. Zhang GZ contributed to conceptualization, supervision the manuscript; Ren ZG contributed to critically revised the manuscript. Zhang GZ and Ren ZG are designated as co-corresponding authors. All authors reviewed and edited the draft and read and agreed to the published version of the manuscript.
AI contribution statement: (1) Only DeepL was used for English language polishing. No ChatGPT, Grammarly or other generative AI tools were applied in this review; (2) No part of the manuscript main text including Abstract, Introduction, Materials and Methods, Results, Discussion and Conclusion was generated by AI tools. All contents were independently written by the authors; (3) AI tool was only used for grammatical correction and language polishing. No AI-assisted translation, data analysis or manuscript writing was performed; (4) No artificial intelligence tool participated in study design, data analysis or result interpretation; and (5) All figures and images in this manuscript are original experimental data processed by the authors, and no AI-generated images are included.
Supported by the National Natural Science Foundation of China, No. 82470654; the Natural Science Foundation Key Project of Henan Province, No. 232300421124; the Henan Zhongyuan Medical Science and Technology Innovation and Development Foundation, No. ZYYC202301ZD; and the Postdoctoral Fellowship Program of the China Postdoctoral Science Foundation, No. GZC20232430.
Conflict-of-interest statement: All authors report no relevant conflicts of interest for this article.
Corresponding author: Zhi-Gang Ren, MD, PhD, Department of Infectious Diseases, State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, No. 46 Jianshe East Road, Zhengzhou 450052, Henan Province, China. fccrenzg@zzu.edu.cn
Received: February 13, 2026 Revised: April 15, 2026 Accepted: June 2, 2026 Published online: November 7, 2026 Processing time: 214 Days and 1.2 Hours
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global health challenge wherein high-protein diets (HPDs) act as a double-edged sword. Building upon the recent systematic review, this review critically examines the dual effects of HPDs on MASLD. Hepatic outcomes depend critically on protein source, intake level, and host metabolic phenotype. Plant-based proteins confer hepatoprotective benefits via gut–liver axis modulation and favorable amino acid signaling, whereas excessive animal protein intake may exacerbate steatosis through mTORC1 activation. However, critical gaps persist: The bioactive peptides in plant proteins remain functionally uncharacterized; evidence-based HPD intake thresholds stratified by disease severity and comorbidities are lacking; and multi-omics findings have yet to translate into clinical practice. Future research must prioritize functional validation of plant-derived bioactives, development of artificial intelligence-driven personalized nutritional algorithms, and long-term randomized controlled trials assessing hard clinical endpoints. Addressing these imperatives will accelerate the transition from generic dietary advice to precision nutritional strategies for MASLD management.
Core Tip: A high-protein diet has dual effects on metabolic dysfunction-associated steatotic liver disease (MASLD), with protein source, intake level, and host metabolic phenotype serving as key regulators. Although previous studies have established a framework involving the gut–liver axis and amino acid pathways, gaps persist in causal mechanisms, intake thresholds, and clinical translation of multiomic findings. Future work should prioritize validating plant-based protein bioactivities, developing personalized algorithms that integrate host–microbiota interactions, and conducting long-term randomized controlled trials for precise MASLD dietary guidance.
