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Adipocyte NMNAT1 expression is essential for nuclear NAD+ biosynthesis but dispensable for regulating thermogenesis and whole-body energy metabolism.
Yamaguchi, Shintaro; Kojima, Daiki; Iqbal, Tooba; Kosugi, Shotaro; Franczyk, Michael P; Qi, Nathan; Sasaki, Yo; Yaku, Keisuke; Kaneko, Kenji; Kinouchi, Kenichiro; Itoh, Hiroshi; Hayashi, Kaori; Nakagawa, Takashi; Yoshino, Jun.
Afiliación
  • Yamaguchi S; Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, 160-8582, Japan; Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Kojima D; Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, 160-8582, Japan.
  • Iqbal T; Department of Molecular and Medical Pharmacology, Faculty of Medicine, University of Toyama, Toyama, Toyama, 930-0194, Japan.
  • Kosugi S; Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, 160-8582, Japan.
  • Franczyk MP; Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Qi N; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109, USA.
  • Sasaki Y; Department of Genetics, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Yaku K; Department of Molecular and Medical Pharmacology, Faculty of Medicine, University of Toyama, Toyama, Toyama, 930-0194, Japan.
  • Kaneko K; Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, 160-8582, Japan.
  • Kinouchi K; Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, 160-8582, Japan.
  • Itoh H; Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, 160-8582, Japan.
  • Hayashi K; Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, 160-8582, Japan.
  • Nakagawa T; Department of Molecular and Medical Pharmacology, Faculty of Medicine, University of Toyama, Toyama, Toyama, 930-0194, Japan.
  • Yoshino J; Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, 160-8582, Japan; Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO, 63110, USA. Electronic address: jyoshino@keio.jp.
Biochem Biophys Res Commun ; 674: 162-169, 2023 09 24.
Article en En | MEDLINE | ID: mdl-37421924
ABSTRACT
Nicotinamide adenine dinucleotide (NAD+) functions as an essential cofactor regulating a variety of biological processes. The purpose of the present study was to determine the role of nuclear NAD+ biosynthesis, mediated by nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1), in thermogenesis and whole-body energy metabolism. We first evaluated the relationship between NMNAT1 expression and thermogenic activity in brown adipose tissue (BAT), a key organ for non-shivering thermogenesis. We found that reduced BAT NMNAT1expression was associated with inactivation of thermogenic gene program induced by obesity and thermoneutrality. Next, we generated and characterized adiponectin-Cre-driven adipocyte-specific Nmnat1 knockout (ANMT1KO) mice. Loss of NMNAT1 markedly reduced nuclear NAD+ concentration by approximately 70% in BAT. Nonetheless, adipocyte-specific Nmnat1 deletion had no impact on thermogenic (rectal temperature, BAT temperature and whole-body oxygen consumption) responses to ß-adrenergic ligand norepinephrine administration and acute cold exposure, adrenergic-mediated lipolytic activity, and metabolic responses to obesogenic high-fat diet feeding. In addition, loss of NMNAT1 did not affect nuclear lysine acetylation or thermogenic gene program in BAT. These results demonstrate that adipocyte NMNAT1 expression is required for maintaining nuclear NAD+ concentration, but not for regulating BAT thermogenesis or whole-body energy homeostasis.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Adipocitos / Termogénesis / Metabolismo Energético / Nicotinamida-Nucleótido Adenililtransferasa Límite: Animals Idioma: En Revista: Biochem Biophys Res Commun Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Adipocitos / Termogénesis / Metabolismo Energético / Nicotinamida-Nucleótido Adenililtransferasa Límite: Animals Idioma: En Revista: Biochem Biophys Res Commun Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos