Ptch2 Deficiency Triggers Lipoma Formation and Adipogenic Transcriptome Reprogramming in Nile tilapia (Oreochromis niloticus)

The Hedgehog (Hh) signaling pathway is a key regulator of adipogenesis and lipid metabolism. However, the specific role of its receptor, Patched2 (Ptch2), in these processes remains unclear. Here, using a CRISPR/Cas9-mediated <i>ptch2</i> homozygous mutation model in Nile tilapia (<i>Oreochromis niloticus</i>), we found that Ptch2 deficiency induced visceral and perirenal lipomatosis characterized by small, multinucleated adipocytes. Comparative adipose transcriptomics revealed pronounced adipogenic reprogramming, with marked upregulation of genes governing de novo lipogenesis (e.g., <i>acaca</i>, <i>fasn</i>), fatty acid desaturation (e.g., <i>scd</i>, <i>fadsd6</i>), and triglyceride synthesis (e.g., <i>dgat2</i>, <i>lpl</i>). Biochemically, mutants exhibited elevated blood glucose and liver transaminases (alanine aminotransferase, aspartate aminotransferase) activity, and reduced alkaline phosphatase activity, indicating systemic metabolic dysregulation and hepatic stress. Our findings demonstrate that loss of Ptch2 triggers lipoma formation and adipogenic transcriptome reprogramming, highlighting its essential role in maintaining adipose tissue homeostasis.