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Hypermetabolism in mice carrying a near-complete human chromosome 21.
Sarver, Dylan C; Xu, Cheng; Rodriguez, Susana; Aja, Susan; Jaffe, Andrew E; Gao, Feng J; Delannoy, Michael; Periasamy, Muthu; Kazuki, Yasuhiro; Oshimura, Mitsuo; Reeves, Roger H; Wong, G William.
Afiliación
  • Sarver DC; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, United States.
  • Xu C; Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, United States.
  • Rodriguez S; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, United States.
  • Aja S; Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, United States.
  • Jaffe AE; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, United States.
  • Gao FJ; Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, United States.
  • Delannoy M; Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, United States.
  • Periasamy M; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States.
  • Kazuki Y; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, United States.
  • Oshimura M; Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States.
  • Reeves RH; The Lieber Institute for Brain Development, Baltimore, United States.
  • Wong GW; Center for Computational Biology, Johns Hopkins University, Baltimore, United States.
Elife ; 122023 05 30.
Article en En | MEDLINE | ID: mdl-37249575
The consequences of aneuploidy have traditionally been studied in cell and animal models in which the extrachromosomal DNA is from the same species. Here, we explore a fundamental question concerning the impact of aneuploidy on systemic metabolism using a non-mosaic transchromosomic mouse model (TcMAC21) carrying a near-complete human chromosome 21. Independent of diets and housing temperatures, TcMAC21 mice consume more calories, are hyperactive and hypermetabolic, remain consistently lean and profoundly insulin sensitive, and have a higher body temperature. The hypermetabolism and elevated thermogenesis are likely due to a combination of increased activity level and sarcolipin overexpression in the skeletal muscle, resulting in futile sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) activity and energy dissipation. Mitochondrial respiration is also markedly increased in skeletal muscle to meet the high ATP demand created by the futile cycle and hyperactivity. This serendipitous discovery provides proof-of-concept that sarcolipin-mediated thermogenesis via uncoupling of the SERCA pump can be harnessed to promote energy expenditure and metabolic health.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Músculo Esquelético / Termogénesis Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Elife Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Músculo Esquelético / Termogénesis Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Elife Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido