Metabolomic Analysis Reveals Changes in Plasma Metabolites in Response to Acute Cold Stress and Their Relationships to Metabolic Health in Cold-Acclimatized Humans.

Zuzana Kovaničová,Miloslav Karhánek,Tímea Kurdiová,Jozef Ukropec,Miroslav Baláž,Christian Wolfrum,Barbara Ukropcová

doi:10.3390/metabo11090619

Abstract

Cold exposure results in activation of metabolic processes required for fueling thermogenesis, potentially promoting improved metabolic health. However, the metabolic complexity underlying this process is not completely understood. We aimed to analyze changes in plasma metabolites related to acute cold exposure and their relationship to cold-acclimatization level and metabolic health in cold-acclimatized humans. Blood samples were obtained before and acutely after 10–15 min of ice-water swimming (<5 °C) from 14 ice-water swimmers. Using mass spectrometry, 973 plasma metabolites were measured. Ice-water swimming induced acute changes in 70 metabolites. Pathways related to amino acid metabolism were the most cold-affected and cold-induced changes in several amino acids correlated with cold-acclimatization level and/or metabolic health markers, including atherogenic lipid profile or insulin resistance. Metabolites correlating with cold-acclimatization level were enriched in the linoleic/α-linolenic acid metabolic pathway. N-lactoyl-tryptophan correlated with both cold-acclimatization level and cold-induced changes in thyroid and parathyroid hormones. Acute cold stress in cold-acclimatized humans induces changes in plasma metabolome that involve amino acids metabolism, while the linoleic and α-linolenic acid metabolism pathway seems to be affected by regular cold exposure. Metabolites related to metabolic health, thermogenic hormonal regulators and acclimatization level might represent prospective molecular factors important in metabolic adaptations to regular cold exposure.

Highlights

Cold exposure results in stimulation of defense mechanisms aimed at maintaining body temperature by reducing heat loss and promoting heat production by muscle shivering or non-shivering thermogenic mechanisms in brown fat, white fat and skeletal muscle
We aimed to explore the regulation of metabolites that could be associated with the thermogenic process by measuring plasma metabolome from coldacclimatized individuals in response to an acute bout of cold stress induced by ice-water swimming using untargeted metabolomics
We aimed to investigate metabolites potentially linking the acute response to cold with the individual metabolic phenotype by evaluating associations between the regulation of metabolite levels and selected markers of metabolic health as well as thyroid and parathyroid hormones that are potentially involved in the regulation of cold-induced thermogenic process in humans [10]

Summary

Introduction

Cold exposure results in stimulation of defense mechanisms aimed at maintaining body temperature by reducing heat loss and promoting heat production by muscle shivering or non-shivering thermogenic mechanisms in brown fat, white fat and skeletal muscle. The high metabolic/thermogenic activity of brown fat can be demonstrated by the accelerated uptake and utilization of various metabolic substrates including glucose, non-esterified fatty acids, succinate and acetate or lactate in parallel with increased facultative energy expenditure [2,3]. The non-shivering production of heat typically requires the onset of lipolysis for the efficient substrate supply of free fatty acids or their derivates from white or brown adipose tissues [4,5]. It is important to further assess the complexity of the metabolic processes activated during cold exposure Understanding of these regulations could provide knowledge necessary for targeted treatment of metabolic diseases such as obesity, dyslipidemia and type 2 diabetes using the therapeutic potential of brown fat

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