02 | Entrainment of skeletal muscle circaldian clock by 2-hydroxybutyrate, a noval exerkine

Taoyue Yang^1|2, L. Matta¹, A. Bartelt^1|3, K. Dyar¹ | ¹Institute for Diabetes and Cancer, Helmholtz Munich, Germany; ²Faculty of Medicine, Ludwig-Maximilian-Universität München, Germany; ³Traslational Nutritional Medicine, Technical University of Munich, Germany.

Abstract

Chronic circadian misalignment as occurs in shift workers and late chronotypes increases metabolic disease risk. Exercise promotes health and metabolic homeostasis in part by entraining and maintaining alignment of circadian clocks in peripheral tissues, especially in skeletal muscle. While exercise-induced metabolites and proteins (so-called exerkines) may play a role entraining skeletal muscle clocks, specific mediators and their mechanism(s) of action remain mostly unknown. In this project we tested and characterized effects of 2-hydroxubutyrate (2-HB), an exerkine we recently identified, and systematically explored whether and how it impacts muscle circadian clocks and metabolism in C2C12 myotubes. Specifically, we profiled 24-hr clock gene (qPCR) and protein levels (Western blot) in cultured myotubes after acute treatment with 2-HB, while also investigating its impact on muscle cell metabolism using oxygraphy (Seahorse) and targeted metabolomics. This project has the potential for identifying an underlying mediator for exercise-induced skeletal muscle clock alignment and holds promise for developing new therapies to mimic some of the effects of exercise on circadian clock regulation.