Ablation of LAT2 Transporter Causes Intramuscular Glutamine Accumulation and Inhibition of Fasting-Induced Proteolysis

Background: The neutral amino acid transporter SLC7A8 (LAT2) has been described as a key regulator of metabolic adaptation.LAT2 mutations in human populations have been linked to the early onset of age-related hearing loss and cataract growth. AsLAT2 was previously found to be highly expressed in sk...

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Detalles Bibliográficos
Autores: Espino-Guarch, Meritxell, Huang, Susie Shih Yin, Vilches, Clara, Prat, Esther, El Nahas, Rana, Missous, Ghalia, Bodoy i Salvans, Susanna, Sathappan, Abbirami, Al-Aghbar, Mohammad Ameen, Mayayo Vallverdú, Clara, Olivé, Montse, Busquets Rius, Sílvia, Sebastián Muñoz, David, Zorzano Olarte, Antonio, Palacín Prieto, Manuel, van Panhuys, Nicholas, Nunes Martínez, Virginia
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/222431
Acceso en línea:https://hdl.handle.net/2445/222431
Access Level:acceso abierto
Palabra clave:Glutamina
Esquelet humà
Envelliment
Glutamine
Human skeleton
Aging
Descripción
Sumario:Background: The neutral amino acid transporter SLC7A8 (LAT2) has been described as a key regulator of metabolic adaptation.LAT2 mutations in human populations have been linked to the early onset of age-related hearing loss and cataract growth. AsLAT2 was previously found to be highly expressed in skeletal muscle, here we characterised its role in the regulation of skeletalmuscle amino acid flux and metabolic adaptation to fasting.Methods: Wild-type (WT) and LAT2 knock-out (LAT2KO) mice were exposed to short- and long-periods of fasting (16 and48 h). The impact of the absence of LAT2 on amino acid content, gene expression, proteolysis activity, muscle tone, and histol-ogy was measured. To characterise the impact on muscle degradation, we tested LAT2 KO mice in cancer-associated cachexia,streptozocin-induced Type-1 diabetes, and ageing models.Results: LAT2KO mice experienced a notable reduction in body weight during fasting (WT:14% and LAT2KO:18%, p = 0.02), witha greater reduction in fat mass (0.5-fold, p = 0.013) and a higher relative retention of muscle mass (1.3-fold, p = 0.0003) comparedwith WT. The absence of LAT2 led to increased intramuscular glutamine (Gln) accumulation (6.3-fold, p < 0.0001), accompanied

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