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<p>Marbling traits serve as a key determinant of meat quality in livestock, with interspecies genetic variations significantly influencing intramuscular fat (IMF) deposition. Through systematic analysis of public databases and cross-species RNA sequencing data from cattle, sheep, and pigs exhibiting divergent IMF levels, we identified <i>PCK2</i> as a conserved regulatory factor governing lipogenesis. Functional analyses demonstrated that targeted <i>PCK2</i> silencing significantly impaired cell cycle dynamics and suppressed adipocyte proliferation, which mechanistically involved transcriptional downregulation of key cell cycle regulators (<i>CCNB1</i>, <i>CCND1</i>, <i>CCNE2</i>) and functional inhibition of critical proliferative mediators (<i>CDK1</i>, <i>CDK2</i>, <i>PCNA</i>). Furthermore, <i>PCK2</i> silencing impaired lipid accumulation by decreasing triglyceride synthesis and lipid droplet formation, while down-regulating adipogenic transcription factors <i>PPARγ</i> and <i>C/EBPα</i>, as well as lipid metabolism factors <i>SCD1</i>, <i>ACSL1</i> and <i>FABP4</i>. Integrated multi-omics analysis revealed <i>PCK2</i> modulates bovine IMF deposition through the regulation of lipolysis in adipocyte. Notably, patatin-like phospholipase domain containing 2 (PNPLA2) suppression as a novel mechanism underlying PCK2-mediated enhancement of bovine intramuscular adipocyte differentiation. These findings establish a molecular framework for understanding <i>PCK2</i>’s regulatory role in marbling beef production.</p> Graphical Abstract <p></p>

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Phosphoenolpyruvate carboxykinase 2 (PCK2) attenuates bovine adipocyte lipolysis through PNPLA2 activity repression

  • 期刊论文

  • 发表日期：

    2025年7月18日

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  • Chao Jiang,
  • Hao Wu,
  • Jiupan Zhang,
  • Yaping Song,
  • Xiaoyu Song,
  • Ruopu Jiao,
  • Sayed Haidar Abbas Raza,
  • Sameer Dinkar Pant,
  • Linsen Zan,
  • Dawei Wei

摘要

Marbling traits serve as a key determinant of meat quality in livestock, with interspecies genetic variations significantly influencing intramuscular fat (IMF) deposition. Through systematic analysis of public databases and cross-species RNA sequencing data from cattle, sheep, and pigs exhibiting divergent IMF levels, we identified PCK2 as a conserved regulatory factor governing lipogenesis. Functional analyses demonstrated that targeted PCK2 silencing significantly impaired cell cycle dynamics and suppressed adipocyte proliferation, which mechanistically involved transcriptional downregulation of key cell cycle regulators (CCNB1, CCND1, CCNE2) and functional inhibition of critical proliferative mediators (CDK1, CDK2, PCNA). Furthermore, PCK2 silencing impaired lipid accumulation by decreasing triglyceride synthesis and lipid droplet formation, while down-regulating adipogenic transcription factors PPARγ and C/EBPα, as well as lipid metabolism factors SCD1, ACSL1 and FABP4. Integrated multi-omics analysis revealed PCK2 modulates bovine IMF deposition through the regulation of lipolysis in adipocyte. Notably, patatin-like phospholipase domain containing 2 (PNPLA2) suppression as a novel mechanism underlying PCK2-mediated enhancement of bovine intramuscular adipocyte differentiation. These findings establish a molecular framework for understanding PCK2’s regulatory role in marbling beef production.

Graphical Abstract