Author(s): LETUKIENĖ, A., GINEVIČIENĖ, V., Institution: FACULTY OF MEDICINE, VILNIUS UNIVERSITY, Country: LITHUANIA, Abstract-ID: 1245

INTRODUCTION:
Individual responses to exercise-based weight loss interventions vary widely, even when physical activity volume and intensity are standardised. While phenotypic and psychological factors may contribute to this variability, genetic predisposition may also play a role. This study aims to investigate phenotypic, psychological, and genetic differences between women who did and did not achieve weight loss following a 12-week physical activity intervention.
METHODS:
35 metabolically healthy, physically inactive women (age 40.06±8.56 years; BMI 31.94±4.23) completed a 12-week physical activity intervention without dietary modification, based on World Health Organisation recommendations. The program included three 50-minute aerobic sessions per week (brisk walking monitored by heart rate) and two resistance training sessions per week. Body composition was assessed pre- and post-intervention. Participants were classified as responders (n=23) or non-responders (n=12). Psychological status was evaluated using the Hospital Anxiety and Depression Scale (HADS) and the Pittsburgh Sleep Quality Index (PSQI). A genome-wide association study (GWAS) was conducted to assess genetic differences between groups.
RESULTS:
Responders showed significant reductions in body weight (−3.27±2,86 kg ), BMI (−1.39±1,48 kg/m²), fat mass (−2,00±2,39 kg), visceral fat (−0,39±0,84 %), and waist-to-hip ratio (−0,01±0,02) . In contrast, non-responders showed increases in body weight (2,53±1,93 kg) and fat mass (1,83±1,13 kg). Sleep quality improved in both groups (10,67-11,86 points), while anxiety scores decreased more markedly in responders (1,94 vs 0,20 points).
GWAS revealed genetic differences between responders and non-responders. In total, 48 SNPs were identified within gene regions. Among these, four were classified as missense variants, two as 3′UTR variants, one as a synonymous variant, five as 2 kb upstream variants, and one as a 500 bp downstream variant. Nine significant variants were mapped to genes involved in metabolic regulation pathways relevant to obesity (p < 0.001). A missense SNP was identified in WDFY4, while the remaining variants were located in coding or regulatory regions of genes associated with insulin/glucose metabolism (ARFGEF3, SLC2A1, CAMK4, MAP3K14, MAP3K14 SNPs) and inflammation-related metabolic control (IL2RA, WDFY4, CSMD1, LILRB2 SNPs). The remaining significant variants were classified into key signaling pathways (Wnt, NF-κB, calcium, etc.) and immune-related pathways.
CONCLUSION:
Despite identical exercise exposure, substantial inter-individual variability in weight loss response was observed. Differences in body composition changes, psychological outcomes, and genetic background may underlie heterogeneous responses to exercise. These findings support personalised approaches to physical activity-based weight management.