Hyperlipidemia in hepatic MED1 deficient mice in response to fasting

MED1 is a key transcription co-activator subunit of the Mediator complex that is essential for RNA polymerase II-dependent transcription. MED1 functions as a co-activator for PPARs and other nuclear receptors and transcription factors, and plays an important role in lipid metabolism. To examine how MED1 might affect plasma lipids, plasma triglyceride, cholesterol levels, and lipoprotein profiles, were measured in MED1^ΔLiv mice fasted for 24, 48 and 72 hours. Histological changes in liver sections from MED1^ΔLiv mice after 72 hours of fasting were also examined using H&E staining. There was no fat accumulation in livers of MED1^ΔLiv mice compared to MED1^fl/fl and PPARα^-/- control mice after 72 hours of fasting. Compared with MED1^fl/fl mice, plasma triglycerides in MED1^ΔLiv mice were significantly increased after 24, 48 and 72 hours of fasting, and plasma cholesterol was significantly increased after 48 and 72 hours of fasting. Lipoprotein profiles were similar in fed MED1^fl/fl and MED1^ΔLiv mice. However, very low density lipoprotein (VLDL) was significantly increased in MED1^ΔLiv mice after 24 hours of fasting. We conclude that, hyperlipidemia in MED1^ΔLiv mice in response to fasting is due to the accumulation of VLDL, which suggests that MED1 plays a pivotal role in the regulation of plasma triglyceride and cholesterol levels.