Metabolites were considered intermediates or end-products of metabolism, passive participants changed by metabolic processes. There is emerging evidence of metabolites, which function to mediate cellular signalling and interorgan crosstalk, regulating local metabolism and systemic physiology. These signals have been termed metabokines.  There is impetus to uncover novel metabokine signalling axes to understand how these are perturbed in metabolic diseases and determine their utility as therapeutic targets.

This talk will provide an overview of our research identifying novel metabokine signals: 

1) A bioactive non-protein β-aminoacid secreted from skeletal muscle during exercise, which induces adipose tissue thermogenesis and liver β-oxidation with anti-obesity and anti-diabetic effects (1).

2) Monocarboxylic acids secreted from thermogenic adipose tissue, which induce a thermogenic phenotype in white adipose tissue and oxidative energy metabolism in skeletal muscle to reduce adiposity, increase energy expenditure and improve glucose and insulin homeostasis in models of obesity and diabetes (2).

3) A lipid released from skeletal muscle in response to lipotoxcity in obesity, which functions as a cell non-autonomous paracrine signal propagating Endoplasmic Reticulum stress with implications in the development of metabolic disease (3).

Our discoveries further our understanding of obesity, and the potential therapeutic role that metabokines may have to treat obesity and related cardiometabolic diseases.