HyperPig - Metabolic health effects associated with muscle hypertrophy in pigs

The main aim of the HyperMet consortium is to detect how hypertrophying muscle reprograms its metabolism and how it affects the metabolism of other tissues by e.g., decreasing the pool of metabolites in circulation. The overall question how fat-to-muscle repartitioning improves metabolic health will be addressed using advanced methods of metabolic research. A major advantage of the pig over rodents is that arteries and veins for all major organs can be easily accessed, giving us the opportunity to investigate how the stimulation of muscle hypertrophy affects the metabolite exchange of muscle, white adipose tissue and many other organs. First, we will induce fat–to muscle repartitioning applying an approach of genetic engineering, generating myostatin deficient Göttingen Minipigs in which prominent muscle hypertrophy is expected. Second, we will apply a pharmacological approach administrating the β2-agonist clenbuterol to achieve fat-to-muscle repartitioning. In both models, metabolite exchange will be assessed from arteriovenous metabolomics in combination with the usage of a [13C] glucose tracer and effects on metabolic health will be assessed in vivo. Amino acid metabolism and specifically the turnover of branched chained amino acids in muscle and fat tissue will be assessed applying a [13C] leucine tracer.