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Annunziata Gaetana Cicatiello, Serena Sagliocchi, Annarita Nappi, Emery Di Cicco, Caterina Miro, Melania Murolo, Mariano Stornaiuolo and Monica Dentice
University of Naples “Federico II”, Italy CEINGE–Biotecnologie Avanzate Scarl, Italy
Posters & Accepted Abstracts: J Endocr Disord Surg
Thyroid hormones (THs) are key metabolic regulators coordinating short- and long-term energy needs. In skeletal muscle, THs modulate energy metabolism in pathophysiological conditions. Indeed, hypothyroidism and hyperthyroidism are leading causes of muscle weakness and strength; however, the metabolic pathways underlying these effects are still poorly understood. Using molecular, biochemical and isotope-tracing approaches combined with mass spectrometry and denervation experiments, we found that THs regulate glutamine metabolism and anaplerotic fluxes by up-regulating the Glutamate Pyruvate Transaminase 2 gene (GPT2). In humans, GPT2 autosomal recessive mutations cause a neurological syndrome characterized by intellectual disability, microcephaly, and progressive motor symptoms. Herein, we demonstrate a new role of TH/GPT2 axis in skeletal muscle, regulating muscle weight and fiber diameter in resting and atrophic conditions and resulting in protection from muscle loss during atrophy. These results describe a new anabolic route by which THs rewire glutamine metabolism towards the maintenance of muscle mass.
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