The Role of NCOR1 and NCOR2 in Skeletal Muscle: Insights from siRNA-mediated Knockdown in C2C12 Cells
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About Me
Hi everyone! My name is Kurian S. Jos — a biology major with a minor in anthropology, originally from Brentwood, CA (the Northern California one, for the record). My research journey began at a virology lab at the University of Minnesota, where I quickly discovered my passion for benchwork and cell culture. That spark led me to join a metabolics lab the following summer as a cell culture assistant, where I spent a year working with hepatocytes. Most recently, I've been part of the Hauck Lab at the University of Minnesota, contributing to research on metabolic targets and therapeutic approaches to addressing the obesity epidemic. After graduation, I plan to pursue medical school, but I'm taking a gap year to dive deeper into my hobbies and gain hands-on, real-world experience in the medical field. When I'm not in the lab or hitting the books, you can find me in the gym — whether that's lifting weights or training in mixed martial arts — or spending time with friends. I've also recently picked up photography and am thoroughly enjoying the journey of learning a new craft!
Abstract
The Nuclear Receptor Co-Repressor (NCOR) complex is an essential regulator of systemic lipid and glucose metabolism. While hepatic Ncor deficiency is known to cause hypoglycemia and impaired adaptation to fasting, how myocellular Ncor1 and Ncor2 regulate inter-organ communication and systemic glucose homeostasis remains unclear. During fasting, the liver and skeletal muscle coordinate to maintain energy homeostasis, with skeletal muscle reducing glucose uptake and releasing amino acids and lactate to support hepatic gluconeogenesis. Based on these interactions, we hypothesized that the Ncor complex regulates the same metabolic genes in skeletal muscle as it does in hepatocytes. To investigate this, we utilized small interfering RNA (siRNA) to knock down Ncor1, Ncor2, and both simultaneously (double knockdown, dKD) in C2C12 mouse myoblast cells. Gene silencing was validated via reverse transcription quantitative PCR (RT-qPCR), and transcriptional responses were evaluated under high and low serum conditions to simulate a starvation response. Under standard high serum conditions, target mRNA expression remained unchanged. However, a 12-hour serum starvation revealed a significantly blunted transcriptional response in dKD cells. In the absence of full Ncor function during starvation, key metabolic genes Got1 and Pdk4 became heavily downregulated, and the normal starvation-induced upregulation of Pgc1a was distinctly blunted. Ultimately, these data suggest that the Ncor complex's genetic targets are highly conserved between skeletal muscle and liver tissues. Future studies will involve understanding genome wide effects using RNA sequencing and myoblast-specific Ncor knockdown in mice to further assess its role in systemic metabolism.
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