Author(s): SUBOCIUS, A., CESANELLI, L., PUTRIUTE, V., CHAILLOU, T., MORO, C., MICKEVICIENE, D., DEGENS, H., KAMANDULIS, S., VENCKUNAS, T., Institution: LITHUANIAN SPORTS UNIVERSITY, Country: LITHUANIA, Abstract-ID: 160

INTRODUCTION:
The ACTN3 R577X polymorphism has been proposed as a genetic factor influencing physiological responses to cold exposure. Indeed, enhanced cold tolerance was detected in XX (α-actinin-3 deficient) compared with RR (α-actinin-3 expressing) individuals (Wyckelsma et al. 2021). However, evidence on ACTN3-dependent metabolic responses to acute cold exposure is still limited, and data in populations with altered metabolic profiles, such as overweight, remain unexplored. Acute cold-water exposure is becoming a popular intervention among health-conscious individuals, and it induces large metabolic, thermogenic, respiratory, cardiovascular, and hormonal responses that may be influenced by genetic variation. This study investigated the influence of the ACTN3 R577X polymorphism on cardiopulmonary, metabolic and lipolytic responses to acute cold exposure in overweight adults.
METHODS:
Overweight (BMI 25–35 kg/m²) but otherwise healthy men and women (total n=300) aged 30–60 years were genotyped for the ACTN3 R577X polymorphism, and then age-matched RR (men n=20, women n=21) and XX (men n=20, women n=19) participants underwent an acute cold exposure: immersion for 15 min into 14 °C water bath to the level of the lower sternum with arms immersed. Expired O2 and CO2 were analyzed, and heart rate and pulmonary ventilation were measured before, during, and after cold water exposure. Subjective sensations were evaluated using standardized scales, and venous blood samples were collected at baseline, pre-bath (i.e., 3 h after baseline), post-bath, and 1 h post-exposure to determine the concentrations of triglycerides, non-esterified fatty acids, glycerol, as well as growth differentiation factor 15 and fibroblast growth factor 21 as potential thermokines (only at pre-bath and post-bath). Data were analyzed using two-way repeated or factorial ANOVA.
RESULTS:
Acute cold exposure increased VO₂, pulmonary ventilation, breathing frequency, heart rate, fat oxidation, and concentrations of circulating lipids and thermokines (time effect: P<0.001 for all markers). No differences between RR and XX individuals were observed for metabolic and cardiopulmonary variables, and subjective sensations (p>0.05), except that XX individuals exhibited a higher mean breathing frequency and a lower mean tidal volume during cold exposure (genotype effect: P=0.010 and P=0.045, respectively). All blood markers responded similarly across genotypes (p>0.05).
CONCLUSION:
In overweight adults, acute cold exposure induces pronounced metabolic and physiological responses that are largely independent of the ACTN3 R577X genotype.

Reference
Wyckelsma VL, Venckunas T, Houweling PJ, et al. Loss of α-actinin-3 during human evolution provides superior cold resilience and muscle heat generation. Am J Hum Genet. 2021 Mar 4;108(3):446-457.