Page 56 - Hormel Report 2023

Dan Xu, PhD
“Our long-term research interest is to elucidate the detailed molecular mechanisms governing adipocyte metabolism, thereby facilitating the development of new therapies for obesity and
its associated metabolic diseases.”
Dan Xu
56 | THE HORMEL INSTITUTE // RNA Regulatory Networks
in Metabolism
ASSISTANT PROFESSOR
UNIVERSITY OF MINNESOTA
The primary focus of our research is to determine the regulation and function of RNA stability in adipocytes and another
branch of my research is to investigate the role
of non-coding RNAs in adipocytes. These proj- ects represent a unique research direction at the intersection between metabolic diseases and RNA biology. We have pursued these areas of research and have discovered several novel regulators including Ybx2 and HuR in adipocyte metabolism. These findings have been published in prestigious journals such as Nature Metabolism, Nature Com- munications, Diabetes, and Journal of Experimental Medicine. Importantly, we have built a compre- hensive research platform centering on metabolic physiology study, complemented by bioinformatic analysis and RNA molecular biology.
Identifying RNA Binding Proteins Involved in the Regulation of Metabolism.
Most of the current understanding of metabolism is at the transcriptional level and in signaling pathways. However, there is no clear understand- ing of how metabolic homeostasis is regulated
at the posttranscriptional level under normal
physiological or pathophysiological conditions. We have identified two RNA-binding proteins
that have novel functions in lipid metabolism. We have demonstrated 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.
Identifying Non-Coding RNA Involved in the Regulation of Metabolism.
While thousands of lncRNAs have been discovered, their biological function remains poorly understood. We identified several hundred lncRNAs conserved between human and mice through RNA-sequencing of different fat depots. Using primary adipocyte culture system, we have identified several functionally important lncRNAs which are required for adipocyte lineage-specific development. To understand their biological function in vivo, we generated several lncRNA knockout and transgenic mice models to characterize their physiological functions.
Circular RNAs (circRNAs) are a new class of non-coding transcripts generated by back-splic- ing and discovered across all eukaryotic tissues, many of which are species-conserved, tissue- specific, and dynamically regulated. However,
their function in adipose biology remains unknown. To bridge this knowledge gap in the field, we analyzed the full transcriptome of visceral and subcutaneous fat in vivo. We discovered thousands of circRNAs uniquely regulated during adipogenesis and obesity, and identified circT- shz2-1 and circArhgap5-2 as indispensable regulators for adipogenesis and adipogenic gene