title: Physiological changes due to mild cooling in healthy lean males of white Caucasian and South Asian descent: A metabolomics study.
abstract: During mild cold exposure, non-shivering thermogenesis increases to maintain core body temperature by increasing utilization of substrates, especially fatty acids (FA), ultimately affecting lipid-associated metabolites. We aimed to investigate whether mild cooling induces changes in other metabolites and whether this response differs between white Caucasians and South Asians, who have a disadvantageous metabolic phenotype. 12 lean male Dutch white Caucasians and 12 matched Dutch South Asians were exposed to mild cold. Before and after 100 min exposure, serum samples were collected for analysis of 163 metabolites and 27 derived parameters using high throughput metabolomics. The overall response to mild cooling between both ethnicities was not different, therefore the data were pooled. After Bonferroni correction, mild cooling significantly changed 44 of 190 (23%) metabolic parameters. Specifically, cooling increased 19 phosphatidylcholine (PC) species, only those containing very long chain FAs, and increased the total class of PC containing mono-unsaturated FAs (+12.5%). Furthermore, cooling increased 10 sphingomyelin species as well as the amino acids glutamine (+18.7%), glycine (+11.6%) and histidine (+10.6%), and decreased short-chain (C3 and C4) acylcarnitines (-17.1% and -19.4%, respectively). In conclusion, mild cooling elicits substantial effects on serum metabolites in healthy males, irrespective of white Caucasian or South Asian ethnicity.
authors.affiliation: Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Kimberly J
authors.initials: KJ
authors.lastname: Nahon
authors.affiliation: Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: m.r.boon@lumc.nl.
authors.forename: Mariëtte R
authors.initials: MR
authors.lastname: Boon
authors.affiliation: Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Leontine E H
authors.initials: LE
authors.lastname: Bakker
authors.affiliation: Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Prehn
authors.affiliation: Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, Neuherberg, Germany; German Center for Diabetes Research, Neuherberg, Germany; Lehrstul für Experimentelle Genetik, Technische Universität München, Freising-Weihenstephan, Germany.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Adamski
authors.affiliation: Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Ingrid M
authors.initials: IM
authors.lastname: Jazet
authors.affiliation: Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands; Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Ko Willems
authors.initials: KW
authors.lastname: van Dijk
authors.affiliation: Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Patrick C N
authors.initials: PC
authors.lastname: Rensen
authors.affiliation: Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands; Epidemiology Section, BESC Department, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Dennis O
authors.initials: DO
authors.lastname: Mook-Kanamori
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People; D001835:Body Weight; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood; D003080:Cold Temperature; D005230:Fatty Acids, Nonesterified / Q000097:blood; D020404:Glycerophospholipids / Q000097:blood; D006801:Humans; D008297:Male; D055432:Metabolomics; D013109:Sphingomyelins / Q000097:blood; D022722:Thermogenesis; D044465:White People; D055815:Young Adult
chemical_list: D005230:Fatty Acids, Nonesterified; D020404:Glycerophospholipids; D013109:Sphingomyelins; C116917:acylcarnitine; D002331:Carnitine
keywords: Lipid metabolism; Metabolomics; Non-shivering thermogenesis