Page 45 - The Hormel Institute 2024 Annual Report

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Our long-term research interest is to better understand the molecular mechanisms governing the metabolism of adipocytes
(cells that store energy as fat), thereby facilitat- ing the development of new therapies for obesity and its associated metabolic diseases.
Our research is a unique intersection between metabolic diseases and RNA biology, focusing on determining the regulation and function of RNA stability and the role of non-coding RNAs in adi- pocytes. We have discovered several novel reg- ulators in adipocyte metabolism—findings that have been published in prestigious journals such as Nature Metabolism, Nature Communications, Diabetes, and Journal of Experimental Medicine.
METABOLIC REGU􏰀TION
The ability to sense nutrient signals and adjust cellular metabolism for environmental adap- tation is essential for cell growth and survival. Organisms respond to nutrient challenges by regulating various biological processes, includ- ing signaling pathways, metabolic enzyme activ- ities, and fuel selection. However, most current understanding of metabolism is focused on the transcriptional level and signaling pathways, with limited insight into how metabolic homeo- stasis is regulated at the posttranscriptional level under normal or pathological conditions. In our efforts to bridge this gap, we have demon- strated Y-box binding protein2 (Ybx2) as a novel regulator in brown fat activation and established Hu-Antigen R (HuR) as an essential repressor during adipocyte development.
UNDERSTANDING ISOFORM USAGE
Recent research has shown that alternative isoform utilization is a crucial regulatory layer for nutrient metabolism. Detailed analysis
of these isoform usage events, which are influenced by nutrient challenges and largely independent of gene expression regulation, has revealed hundreds of conserved isoform events. Hu-Antigen R (HuR) emerged as the predom- inant orchestrator of the isoform network in adipocytes.
IDENTIFYING NON-CODING RNA
While thousands of long non-coding RNAs (lncRNAs) have been discovered, their biolog- ical function remains poorly understood. We identified several hundred lncRNAs conserved between humans and murine models and several functionally important lncRNAs required for adipocyte lineage-specific development and generated several different models to elucidate their physiological functions in vivo.
In adipose biology, the function of circular RNAs (circRNAs), remains unknown. We analyzed the full transcriptome of visceral and subcutaneous fat in vivo, discovering thousands of circRNAs uniquely regulated during adipogenesis and obesity, and identified indispensable regulators for adipogenesis (the process of forming fat cells) and adipogenic gene program mainte- nance in mature adipocytes. To the best of our knowledge, our results provide the first evidence that circRNAs serve as important regulators in adipocyte differentiation and metabolism.