Turning Fat to Muscle by Activating Muscle-Specific Genes

Overview

Obesity is a global health issue that impacts individuals of all ages, backgrounds, and socioeconomic statuses. Its consequences are severe, encompassing an elevated risk of chronic diseases like heart disease, diabetes, and certain types of cancer. Moreover, it leads to a diminished quality of life and a higher cost of healthcare. Thus, it is essential to identify the factors contributing to obesity and explore effective prevention and treatment strategies. Recently, we investigated the differentially expr essed genes (DEGs) between inguinal white adipose tissue (iWAT) and thigh adipose tissue (tAT). From these DEGs, two muscle-specific genes, Myod1 and Myf6, exhibited especially high expression levels in tAT. This led us to hypothesize that the upregulation of Myod1 and Myf6 could in duce 'browning' in white adipose tissue, thereby altering its metabolic function from energy storage to expenditure. To test this hypothesis, we utilized the CRISPRdCas9 -VPR system, designing five guide RNAs (gRNAs) for both Myod 1 and Myf6, packaging them into lentiviruses and introducing them into C3H10T1/2 cellderived adipocytes. Further qPCR analysis demonstrated the successful activation of Myod1 and Myf6 in the transduced adipocytes, which intriguingly coincided with an upreg ulation in two other myogenic genes of Myog, and Acta1, while simultaneously downregulating various adipogenic markers such as Adipoq, Cebpa, Cebpb, and Pparg1. Additionally, Oil Red-Ostaining revealed a decrease in lipid droplets within the white adipocytes, indicating the 'browning' of said adipocytes. This project establishes that the upregulation of Myod1 and Myf6 plays a pivotal role in the 'browning' of WAT, thereby offering promising prospects for the development of anti - obesity therapies.

Competition history

• JSHS 2024 Category not listed

Resources

• National JSHS abstract book ↗

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