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Paracardial fat remodeling affects systemic metabolism through alcohol dehydrogenase 1.
Petrosino, Jennifer M; Longenecker, Jacob Z; Ramkumar, Srinivasagan; Xu, Xianyao; Dorn, Lisa E; Bratasz, Anna; Yu, Lianbo; Maurya, Santosh; Tolstikov, Vladimir; Bussberg, Valerie; Janssen, Paul Ml; Periasamy, Muthu; Kiebish, Michael A; Duester, Gregg; von Lintig, Johannes; Ziouzenkova, Ouliana; Accornero, Federica.
Afiliación
  • Petrosino JM; Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.
  • Longenecker JZ; Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.
  • Ramkumar S; Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio, USA.
  • Xu X; Department of Biomedical Engineering, Dorothy M. Davis Heart and Lung Research Institute.
  • Dorn LE; Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.
  • Bratasz A; Small Animal Imaging Core.
  • Yu L; Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University, Columbus, Ohio, USA.
  • Maurya S; Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.
  • Tolstikov V; BERG, Precision Medicine Department, Framingham, Massachusetts, USA.
  • Bussberg V; BERG, Precision Medicine Department, Framingham, Massachusetts, USA.
  • Janssen PM; Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.
  • Periasamy M; Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.
  • Kiebish MA; Department of Internal Medicine, University of Central Florida, Orlando, Florida, USA.
  • Duester G; BERG, Precision Medicine Department, Framingham, Massachusetts, USA.
  • von Lintig J; Development, Aging, and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA.
  • Ziouzenkova O; Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio, USA.
  • Accornero F; Department of Human Sciences, College of Education and Human Ecology, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA.
J Clin Invest ; 131(4)2021 02 15.
Article en En | MEDLINE | ID: mdl-33586683
The relationship between adiposity and metabolic health is well established. However, very little is known about the fat depot, known as paracardial fat (pCF), located superior to and surrounding the heart. Here, we show that pCF remodels with aging and a high-fat diet and that the size and function of this depot are controlled by alcohol dehydrogenase 1 (ADH1), an enzyme that oxidizes retinol into retinaldehyde. Elderly individuals and individuals with obesity have low ADH1 expression in pCF, and in mice, genetic ablation of Adh1 is sufficient to drive pCF accumulation, dysfunction, and global impairments in metabolic flexibility. Metabolomics analysis revealed that pCF controlled the levels of circulating metabolites affecting fatty acid biosynthesis. Also, surgical removal of the pCF depot was sufficient to rescue the impairments in cardiometabolic flexibility and fitness observed in Adh1-deficient mice. Furthermore, treatment with retinaldehyde prevented pCF remodeling in these animals. Mechanistically, we found that the ADH1/retinaldehyde pathway works by driving PGC-1α nuclear translocation and promoting mitochondrial fusion and biogenesis in the pCF depot. Together, these data demonstrate that pCF is a critical regulator of cardiometabolic fitness and that retinaldehyde and its generating enzyme ADH1 act as critical regulators of adipocyte remodeling in the pCF depot.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pericardio / Alcohol Deshidrogenasa / Tejido Adiposo / Mitocondrias Cardíacas / Obesidad Límite: Animals Idioma: En Revista: J Clin Invest Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pericardio / Alcohol Deshidrogenasa / Tejido Adiposo / Mitocondrias Cardíacas / Obesidad Límite: Animals Idioma: En Revista: J Clin Invest Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos