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<p>Fat accumulation and tetrodotoxin (TTX) resistance are critical adaptive traits that enable pufferfish to cope with migratory behavior and environmental fluctuations. Here, we integrate whole-genome sequencing, transcriptomic, and electrophysiological analyses to investigate the molecular mechanisms underlying fatty acid metabolism and TTX tolerance in <i>Takifugu fasciatus</i>. A high-quality genome assembly (372.8 Mb, with 94.9% of sequences anchored to 22 chromosomes) suggests that the ancestral freshwater population of <i>T. fasciatus</i> adapted to marine environments approximately 130,000 years ago. <i>DGAT2</i> and <i>GPAT3</i> are identified as key regulators of lipid biosynthesis. RNA interference (RNAi)-mediated silencing of these genes significantly reduces hepatic triglyceride levels and lipid droplet accumulation. Four amino acid substitutions are found in Na<sub>V</sub>1.4 channels of <i>T. fasciatus</i>, with a D400E mutation in Domain I that significantly enhancing TTX resistance. These findings highlight conserved lipid metabolism pathways and Na<sub>V</sub> channel mutations as key evolutionary strategies for environmental adaptation in pufferfish.</p><p></p>

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Defense mechanisms of Takifugu fasciatus in fatty liver adaptation and tetrodotoxin resistance

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月16日

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  • Xuechun Zang,
  • Tao Wang,
  • Ruhua Shang,
  • Danqing Yin,
  • Yihui Bi,
  • Peng Chu,
  • Cheng Zhao,
  • Yuxi Liu,
  • Shanmei Zou,
  • Shaowu Yin

摘要

Fat accumulation and tetrodotoxin (TTX) resistance are critical adaptive traits that enable pufferfish to cope with migratory behavior and environmental fluctuations. Here, we integrate whole-genome sequencing, transcriptomic, and electrophysiological analyses to investigate the molecular mechanisms underlying fatty acid metabolism and TTX tolerance in Takifugu fasciatus. A high-quality genome assembly (372.8 Mb, with 94.9% of sequences anchored to 22 chromosomes) suggests that the ancestral freshwater population of T. fasciatus adapted to marine environments approximately 130,000 years ago. DGAT2 and GPAT3 are identified as key regulators of lipid biosynthesis. RNA interference (RNAi)-mediated silencing of these genes significantly reduces hepatic triglyceride levels and lipid droplet accumulation. Four amino acid substitutions are found in NaV1.4 channels of T. fasciatus, with a D400E mutation in Domain I that significantly enhancing TTX resistance. These findings highlight conserved lipid metabolism pathways and NaV channel mutations as key evolutionary strategies for environmental adaptation in pufferfish.