Cold Exposure Distinctively Modulates Parathyroid and Thyroid Hormones in Cold-Acclimatized and Non-Acclimatized Humans

Abstract

Cold-induced activation of thermogenesis modulates energy metabolism, but the role of humoral mediators is not completely understood. We aimed to investigate the role of parathyroid and thyroid hormones in acute and adaptive response to cold in humans. Examinations were performed before/after 15 minutes of ice-water swimming (n = 15) or 120 to 150 minutes of cold-induced nonshivering thermogenesis (NST) applied to cold-acclimatized (n = 6) or non-acclimatized (n = 11) individuals. Deep-neck brown adipose tissue (BAT) was collected from non-acclimatized patients undergoing elective neck surgery (n = 36). Seasonal variations in metabolic/hormonal parameters of ice-water swimmers were evaluated. We found that in ice-water swimmers, PTH and TSH increased and free T3, T4 decreased after a 15-minute winter swim, whereas NST-inducing cold exposure failed to regulate PTH and free T4 and lowered TSH and free T3. Ice-water swimming-induced increase in PTH correlated negatively with systemic calcium and positively with phosphorus. In non-acclimatized men, NST-inducing cold decreased PTH and TSH. Positive correlation between systemic levels of PTH and whole-body metabolic preference for lipids as well as BAT volume was found across the 2 populations. Moreover, NST-cooling protocol-induced changes in metabolic preference for lipids correlated positively with changes in PTH. Finally, variability in circulating PTH correlated positively with UCP1/UCP1, PPARGC1A, and DIO2 in BAT from neck surgery patients. Our data suggest that regulation of PTH and thyroid hormones during cold exposure in humans varies by cold acclimatization level and/or cold stimulus intensity. Possible role of PTH in NST is indicated by its positive relationships with whole-body metabolic preference for lipids, BAT volume, and UCP1 content.

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

“…Notably, ice-water swimming-induced change in all the aforementioned fatty acids enriched in the LA and ALA pathway correlated positively with the cold-induced change in parathyroid hormone, which is one of the emerging potential mediators of the thermogenic process [ 10 , 29 , 30 ]. PTH has direct lipolytic action and we have previously shown it is markedly induced by ice-water swimming in humans [ 10 ].…”

“…This approach allowed us not only to measure relative changes in the pool of hundreds of circulating metabolites, but also to identify pathways regulated in response to cold stress that might reveal robust changes in the whole-body energy metabolism that promote efficient production of heat. Furthermore, 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 ].…”

Metabolic effects of brown fat in transitioning from hyperthyroidism to euthyroidism

“…Some adult human studies also demonstrated a higher level of thyroid hormone nuclear receptors expressed in activated BAT, implying a role for thyroid hormone in the regulation of BAT activation ( 49 ). Many previous studies relating the thyroid with BAT were conducted using cold stimulation ( 50 , 51 ). Notably, Evie et al ( 52 ) reported that BAT activity significantly increased in the subclinical hyperthyroid state compared to the hypothyroid state.…”

A Possible Preventive Role of Physically Active Lifestyle during the SARS-CoV-2 Pandemic; Might Regular Cold-Water Swimming and Exercise Reduce the Symptom Severity of COVID-19?

“…Mitochondrial functions and capacity can also be enhanced by brown adipose tissue, which is metabolically activated by cold exposure [43,44]. Recently, Kovaničová et al [45] have reported that cold-acclimatized ice-water swimmers respond to cold by non-shivering thermogenesis mediated by higher fat oxidation than controls. However, it is important to note the ambient temperature (e.g., water).…”

“…Swimming in mild-cold water (20 • C) does not activate brown adipose tissue in mice [46]. Similarly, mild cold exposure in humans does not stimulate thyroid hormone circulation [45], which has been shown to induce adipose tissue browning [47]. We assumed that the novice cold-water swimmers might have a lower adaptation to cold than experienced swimmers, and therefore, more than five hundred first-season cold-water swimmers were excluded from our final analysis.…”