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

doi:10.1016/j.celrep.2023.113131

Cold-stimulated brown adipose tissue activation is related to changes in serum metabolites relevant to NAD⁺ metabolism in humans

Cell Rep. 2023 Sep 26;42(9):113131. doi: 10.1016/j.celrep.2023.113131. Epub 2023 Sep 13.

Authors

Mueez U-Din¹, Vanessa D de Mello², Marjo Tuomainen², Juho Raiko³, Tarja Niemi⁴, Tobias Fromme⁵, Anton Klåvus², Nadine Gautier⁶, Kimmo Haimilahti⁷, Marko Lehtonen⁸, Karsten Kristiansen⁹, John W Newman¹⁰, Kirsi H Pietiläinen¹¹, Jussi Pihlajamäki¹², Ez-Zoubir Amri⁶, Martin Klingenspor⁵, Pirjo Nuutila¹³, Eija Pirinen¹⁴, Kati Hanhineva¹⁵, Kirsi A Virtanen¹⁶

Affiliations

¹ Turku PET Centre, Turku University Hospital, Turku, Finland; Turku PET Centre, University of Turku, Turku, Finland.
² Department of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
³ Turku PET Centre, Turku University Hospital, Turku, Finland.
⁴ Department of Surgery, Turku University Hospital, Turku, Finland.
⁵ 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.
⁶ Université Côte d'Azur, CNRS, Inserm, iBV, Nice, France.
⁷ 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.
⁸ Department of Pharmacy, University of Eastern Finland, Kuopio, Finland.
⁹ Department of Biology, University of Copenhagen, Copenhagen, Denmark.
¹⁰ 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.
¹¹ 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.
¹² 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.
¹³ Turku PET Centre, Turku University Hospital, Turku, Finland; Turku PET Centre, University of Turku, Turku, Finland; Department of Endocrinology, Turku University Hospital, Turku, Finland.
¹⁴ 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.
¹⁵ 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.
¹⁶ 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. Electronic address: kirsi.virtanen@utu.fi.

PMID: 37708023
DOI: 10.1016/j.celrep.2023.113131

Abstract

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.

Keywords: BAT; CP: Metabolism; NAD(+); cold exposure; human brown adipose tissue; nicotinamide; tryptophan.