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

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

Chair of Molecular Nutritional Medicine

Turku University Hospital
University of Turku and Turku University Hospital
University of Kuopio
Technical University of Munich
CNRS
University of Helsinki
University of Copenhagen
Economic Research Service
University of California, Davis
Helsinki University Central Hospital
Kuopion Yliopistollinen sairaala
Faculty of Medicine
Chalmers University of Technology

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

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.

Original language	English
Article number	113131
Journal	Cell Reports
Volume	42
Issue number	9
DOIs	https://doi.org/10.1016/j.celrep.2023.113131
State	Published - 26 Sep 2023

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

BAT
CP: Metabolism
NAD
cold exposure
human brown adipose tissue
nicotinamide
tryptophan

Access to Document

10.1016/j.celrep.2023.113131

Cite this

U-Din, M., de Mello, V. D., Tuomainen, M., Raiko, J., Niemi, T., Fromme, T., Klåvus, A., Gautier, N., Haimilahti, K., Lehtonen, M., Kristiansen, K., Newman, J. W., Pietiläinen, K. H., Pihlajamäki, J., Amri, E. Z., Klingenspor, M., Nuutila, P., Pirinen, E., Hanhineva, K., & Virtanen, K. A. (2023). Cold-stimulated brown adipose tissue activation is related to changes in serum metabolites relevant to NAD⁺ metabolism in humans. Cell Reports, 42(9), Article 113131. https://doi.org/10.1016/j.celrep.2023.113131

@article{38ca33f6a5104922b46f99b4ed18ac45,

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

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",

author = "Mueez U-Din and \{de Mello\}, \{Vanessa D.\} and Marjo Tuomainen and Juho Raiko and Tarja Niemi and Tobias Fromme and Anton Kl{\aa}vus and Nadine Gautier and Kimmo Haimilahti and Marko Lehtonen and Karsten Kristiansen and Newman, \{John W.\} and Pietil{\"a}inen, \{Kirsi H.\} and Jussi Pihlajam{\"a}ki and Amri, \{Ez Zoubir\} and Martin Klingenspor and Pirjo Nuutila and Eija Pirinen and Kati Hanhineva and Virtanen, \{Kirsi A.\}",

note = "Publisher Copyright: {\textcopyright} 2023 The Author(s)",

year = "2023",

month = sep,

day = "26",

doi = "10.1016/j.celrep.2023.113131",

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U-Din, M, de Mello, VD, Tuomainen, M, Raiko, J, Niemi, T, Fromme, T, Klåvus, A, Gautier, N, Haimilahti, K, Lehtonen, M, Kristiansen, K, Newman, JW, Pietiläinen, KH, Pihlajamäki, J, Amri, EZ, Klingenspor, M, Nuutila, P, Pirinen, E, Hanhineva, K & Virtanen, KA 2023, 'Cold-stimulated brown adipose tissue activation is related to changes in serum metabolites relevant to NAD⁺ metabolism in humans', Cell Reports, vol. 42, no. 9, 113131. https://doi.org/10.1016/j.celrep.2023.113131

TY - JOUR

T1 - Cold-stimulated brown adipose tissue activation is related to changes in serum metabolites relevant to NAD+ metabolism in humans

AU - U-Din, Mueez

AU - de Mello, Vanessa D.

AU - Tuomainen, Marjo

AU - Raiko, Juho

AU - Niemi, Tarja

AU - Fromme, Tobias

AU - Klåvus, Anton

AU - Gautier, Nadine

AU - Haimilahti, Kimmo

AU - Lehtonen, Marko

AU - Kristiansen, Karsten

AU - Newman, John W.

AU - Pietiläinen, Kirsi H.

AU - Pihlajamäki, Jussi

AU - Amri, Ez Zoubir

AU - Klingenspor, Martin

AU - Nuutila, Pirjo

AU - Pirinen, Eija

AU - Hanhineva, Kati

AU - Virtanen, Kirsi A.

PY - 2023/9/26

Y1 - 2023/9/26

N2 - 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.

AB - 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.

KW - BAT

KW - CP: Metabolism

KW - NAD

KW - cold exposure

KW - human brown adipose tissue

KW - nicotinamide

KW - tryptophan

UR - https://www.scopus.com/pages/publications/85171357961

U2 - 10.1016/j.celrep.2023.113131

DO - 10.1016/j.celrep.2023.113131

M3 - Article

C2 - 37708023

AN - SCOPUS:85171357961

SN - 2639-1856

VL - 42

JO - Cell Reports

JF - Cell Reports

IS - 9

M1 - 113131

ER -