FUS, a novel negative regulator of adipogenesis

Abstract:

Introduction: As an RNA-binding protein, FUS has been extensively studied in neurodegenerative diseases and cancers, with a significant gap in knowledge regarding its role in metabolism, especially in adipose related obesity. The occurrence and development of obesity are closely related to the adipogenic differentiation of Adipose-Derived Stem Cells (ADSCs) in adipose tissue. Proliferation of ADSC is a prerequisite for adipogenic differentiation. In this study, we aim to explore the roles of FUS in adipogenesis function.

Methods: Human visceral adipose tissue from omentum were collected and primary ADSCs were isolated and cultured in vitro. We detected the expression of FUS in omental adipose tissue from obese and normal-weighted patients using qPCR and WB methods. During the differentiation of ADSC into mature adipocytes, qPCR and Western Blot (WB) were applied to evaluate the expression of FUS. Oil-red O staining and WB were conducted to evaluate the lipid accumulation and key adipogenic regulators. Research on mechanisms involves RNA sequencing of enriched RNA after RNA immunoprecipitation, in combination with transcriptome sequencing from cells overexpressing FUS. RNA stability is determined by using qPCR to measure the expression level of RNA with Actinomycin D.

Results: We found a significant downregulation in FUS expression from omental adipose tissue in obese patients. A gradual decrease of FUS during the adipogenic differentiation of ADSCs in vitro. FUS can bind to CCNB2 mRNA, leading to a decrease in mRNA expression. Moreover, it has been observed to disrupt the stability of CCNB2's mRNA.

Conclusion: FUS regulates proliferative genes to hinder the adipogenic fate of ADSCs, thereby participating in the occurrence and development of obesity, providing a new target for obesity and its related metabolic dysfunction prevention and treatment.

Audience take away notes:

• In this study, a new adipogenic-regulating factor has been discovered.
• This study can inspire new ideas and broaden research perspectives.
• This gene is beneficial as a potential new target for precision treatment of obesity.

Biography:

Dr. Chen studied Clinical Medicine at the Sun Yat-sen University, China and graduated as MS in 2017. She then joined the research group of Prof. Li at the Department of Endocrinology and Diabetes Center, The First Affliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China. She received her PhD degree in 2022 at the same institution. After that, she became a clinical physician with a research-oriented mindset. During her clinical practice, she leveraged her expertise in the field to conduct scientific researches. She has published multiple articles on adipose and stem cells and is passionate about this field of study.