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ORIGINAL RESEARCH article

Front. Physiol.

Sec. Aquatic Physiology

This article is part of the Research TopicInnovations in Aquatic Animal Nutrition and Sustainable Feed DevelopmentView all 3 articles

The multi-protective role of dietary betaine in largemouth bass (Micropterus salmoides): Coordinating antioxidant, inflammatory, and metabolic homeostasis under high-fat diet stress

Provisionally accepted
Yi-Jia  LiuYi-Jia Liu1Jian  GuoJian Guo1Chang-Da  LiChang-Da Li2Siyin  HanSiyin Han3*Lu  CaiLu Cai1*
  • 1Zhejiang Ocean University, Zhoushan, China
  • 2Wenzhou Dongtou District Marine and Fisheries Development Research Center, Wenzhou, China
  • 3Henan University of Technology, Zhengzhou, China

The final, formatted version of the article will be published soon.

Abstract Intensive aquaculture frequently utilizes high-fat diets (HF) as a cost-effective strategy to promote growth and spare protein, yet this practice often induces metabolic disorders such as hepatic steatosis, oxidative stress, and chronic inflammation in carnivorous fish. This study investigated the protective effects and underlying mechanisms of dietary betaine in juvenile largemouth bass (Micropterus salmoides) fed an HF. Four isonitrogenous diets were formulated: a normal-fat control (Control), a high-fat diet (HF), and two high-fat diets supplemented with 0.5% (HFB0.5) or 1.0% (HFB1) betaine. After an 8-week feeding trial, the HF group exhibited significantly impaired growth performance, digestive enzyme activities, and antioxidant capacity, alongside increased lipid peroxidation, dyslipidemia, and hepatic pro-inflammatory cytokine expression. Betaine supplementation effectively restored growth performance and feed efficiency to control levels. It counteracted HF-induced digestive impairment and significantly enhanced lipase activity. Betaine robustly activated the hepatic Nrf2-Keap1 pathway, upregulating antioxidant genes (nrf2, sod1, cat, gpx, ho-1, gr) and enhancing corresponding enzyme activities, thereby reducing oxidative stress. It also ameliorated dyslipidemia, significantly lowering serum triglycerides and LDL-C while elevating HDL-C. Transcriptional analysis revealed that betaine reprogrammed hepatic lipid metabolism by upregulating genes related to fatty acid oxidation (pparα, cpt-1) and lipolysis (lpl, hsl) while suppressing lipogenesis (srebp-1, fas). Furthermore, betaine restored inflammatory homeostasis by suppressing pro-inflammatory cytokines (tnf-α, il-1β) and enhancing anti-inflammatory mediators (tgf-β1, il-10). In conclusion, dietary betaine effectively coordinates antioxidant, metabolic, and anti-inflammatory responses, establishing it as a multi-functional feed additive that mitigates HF-induced metabolic stress and promotes overall health in M. salmoides.

Keywords: Betaine, Micropterus salmoides, high-fat diet, antioxidant capacity, Lipid Metabolism, Inflammatory Response

Received: 09 Nov 2025; Accepted: 27 Nov 2025.

Copyright: © 2025 Liu, Guo, Li, Han and Cai. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Siyin Han
Lu Cai

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