Cold-stimulated brown adipose tissue activation is related to changes in serum metabolites relevant to NAD+ metabolism in humans
Mueez U-Din,
Vanessa D. de Mello,
Marjo Tuomainen,
Juho Raiko,
Tarja Niemi,
Tobias Fromme,
Anton Klåvus,
Nadine Gautier,
Kimmo Haimilahti,
Marko Lehtonen,
Karsten Kristiansen,
John W. Newman,
Kirsi H. Pietiläinen,
Jussi Pihlajamäki,
Ez-Zoubir Amri,
Martin Klingenspor,
Pirjo Nuutila,
Eija Pirinen,
Kati Hanhineva,
Kirsi A. Virtanen
Affiliations
Mueez U-Din
Turku PET Centre, Turku University Hospital, Turku, Finland; Turku PET Centre, University of Turku, Turku, Finland
Vanessa D. de Mello
Department of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
Marjo Tuomainen
Department of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
Juho Raiko
Turku PET Centre, Turku University Hospital, Turku, Finland
Tarja Niemi
Department of Surgery, Turku University Hospital, Turku, Finland
Tobias Fromme
Chair for Molecular Nutritional Medicine, Technical University of Munich, Freising, Germany; EKFZ – Else Kröner Fresenius Center for Nutritional Medicine, Technical University of Munich, Freising, Germany; ZIEL – Institute for Food & Health, Technical University of Munich, Freising, Germany
Anton Klåvus
Department of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
Nadine Gautier
Université Côte d'Azur, CNRS, Inserm, iBV, Nice, France
Kimmo Haimilahti
Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland; Research Program for Stem Cells and Metabolism, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland
Marko Lehtonen
Department of Pharmacy, University of Eastern Finland, Kuopio, Finland
Karsten Kristiansen
Department of Biology, University of Copenhagen, Copenhagen, Denmark
John W. Newman
Obesity and Metabolism Research Unit, USDA-ARS Western Human Nutrition Research Center, Davis, CA, USA; West Coast Metabolomics Center, Davis Genome Center, University of California, Davis, Davis, CA 95616, USA; Department of Nutrition, University of California, Davis, Davis, CA 95616, USA
Kirsi H. Pietiläinen
Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Obesity Center, Abdominal Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
Jussi Pihlajamäki
Department of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland; Department of Endocrinology and Clinical Nutrition, Department of Medicine, Kuopio University Hospital, Kuopio, Finland
Ez-Zoubir Amri
Université Côte d'Azur, CNRS, Inserm, iBV, Nice, France
Martin Klingenspor
Chair for Molecular Nutritional Medicine, Technical University of Munich, Freising, Germany; EKFZ – Else Kröner Fresenius Center for Nutritional Medicine, Technical University of Munich, Freising, Germany; ZIEL – Institute for Food & Health, Technical University of Munich, Freising, Germany
Pirjo Nuutila
Turku PET Centre, Turku University Hospital, Turku, Finland; Turku PET Centre, University of Turku, Turku, Finland; Department of Endocrinology, Turku University Hospital, Turku, Finland
Eija Pirinen
Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland; Research Unit for Internal Medicine, Faculty of Medicine, University of Oulu, 90220 Oulu, Finland
Kati Hanhineva
Department of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland; Department of Life Technologies, Food Chemistry and Food Development Unit, University of Turku, Turku, Finland; Department of Biology and Biological Engineering, Division of Food and Nutrition Science, Chalmers University of Technology, Gothenburg, Sweden
Kirsi A. Virtanen
Turku PET Centre, Turku University Hospital, Turku, Finland; Turku PET Centre, University of Turku, Turku, Finland; Department of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland; Department of Endocrinology and Clinical Nutrition, Department of Medicine, Kuopio University Hospital, Kuopio, Finland; Department of Endocrinology, Turku University Hospital, Turku, Finland; Corresponding author
Summary: Cold-induced brown adipose tissue (BAT) activation is considered to improve metabolic health. In murine BAT, cold increases the fundamental molecule for mitochondrial function, nicotinamide adenine dinucleotide (NAD+), but limited knowledge of NAD+ metabolism during cold in human BAT metabolism exists. We show that cold increases the serum metabolites of the NAD+ salvage pathway (nicotinamide and 1-methylnicotinamide) in humans. Additionally, individuals with cold-stimulated BAT activation have decreased levels of metabolites from the de novo NAD+ biosynthesis pathway (tryptophan, kynurenine). Serum nicotinamide correlates positively with cold-stimulated BAT activation, whereas tryptophan and kynurenine correlate negatively. Furthermore, the expression of genes involved in NAD+ biosynthesis in BAT is related to markers of metabolic health. Our data indicate that cold increases serum tryptophan conversion to nicotinamide to be further utilized by BAT. We conclude that NAD+ metabolism is activated upon cold in humans and is probably regulated in a coordinated fashion by several tissues.
