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

## TL;DR

Disabling the Ptch2 gene in Nile tilapia causes fatty tumor growth and changes in fat-related genes, leading to metabolic issues.

## Contribution

This study identifies Ptch2 as a key regulator of fat tissue development and lipid metabolism in fish.

## Key findings

- Ptch2 deficiency in Nile tilapia causes lipoma formation and adipogenic gene upregulation.
- Mutant fish show elevated blood glucose and liver stress markers, indicating metabolic dysregulation.
- Transcriptomic analysis reveals reprogramming of genes involved in fat synthesis and storage.

## Abstract

This study explored the role of the gene ptch2 in adipogenesis and lipid metabolism in Nile tilapia. Mutation of ptch2 led to the formation of lipomas (benign fatty tumors) in the body cavity and around the kidneys. Analysis of fat tissue showed significant changes in gene expression, especially the upregulation of genes responsible for fat synthesis and storage. The mutant fish also exhibited higher blood glucose and signs of liver stress, indicating whole-body metabolic disturbances. These findings reveal that Ptch2 plays a key role in regulating normal fat tissue formation and lipid metabolism, providing a new model for studying related metabolic disorders.

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 ptch2 homozygous mutation model in Nile tilapia (Oreochromis niloticus), 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., acaca, fasn), fatty acid desaturation (e.g., scd, fadsd6), and triglyceride synthesis (e.g., dgat2, lpl). 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.