Genetics of Exercise and Diet-Induced Fat Loss Efficiency: A Systematic Review

There is a wide range of individual variability in the change of body weight in response to exercise, and this variability partly depends on genetic factors. The study aimed to determine DNA polymorphisms associated with fat loss efficiency in untrained women with normal weight in response to a 12-week aerobic training program using the GWAS approach, followed by a cross-sectional study in athletes. The study involved 126 untrained young Polish women (age 21.4 ± 1.7 years; body mass index (BMI): 21.7 (2.4) kg/m²) and 550 Russian athletes (229 women, age 23.0 ± 4.1; 321 men, age 23.9 ± 4.7). We identified one genome-wide significant polymorphism (rs116143768) located in the ACSL1 gene (acyl-CoA synthetase long-chain family member 1, implicated in fatty acid oxidation), with a rare T allele associated with higher fat loss efficiency in Polish women (fat mass decrease: CC genotype (n = 122) −3.8%; CT genotype (n = 4) −31.4%; p = 1.18 × 10⁻⁹). Furthermore, male athletes with the T allele (n = 7) had significantly lower BMI (22.1 (3.1) vs. 25.3 (4.2) kg/m², p = 0.046) than subjects with the CC genotype (n = 314). In conclusion, we have shown that the rs116143768 T allele of the ACSL1 gene is associated with higher fat loss efficiency in response to aerobic training in untrained women and lower BMI in physically active men.

The kidney and brain expressed protein (KIBRA) plays an important role in synaptic plasticity. Carriers of the T allele of the KIBRA (WWC1) gene rs17070145 C/T polymorphism have been reported to have enhanced spatial ability and to outperform individuals with the CC genotype in working memory tasks. Since ability in chess and science is directly related to spatial ability and working memory, we hypothesized that the KIBRA T allele would be positively associated with chess player status and PhD status in science. We tested this hypothesis in a study involving 2479 individuals (194 chess players, 119 PhD degree holders in STEM fields, and 2166 controls; 1417 males and 1062 females) from three ethnicities (236 Kazakhs, 1583 Russians, 660 Tatars). We found that frequencies of the T allele were significantly higher in Kazakh (66.9 vs. 55.1%; p = 0.024), Russian (44.8 vs. 32.0%; p = 0.0027), and Tatar (51.5 vs. 41.8%; p = 0.035) chess players compared with ethnically matched controls (meta-analysis for CT/TT vs. CC: OR = 2.05, p = 0.0001). In addition, none of the international chess grandmasters (ranked among the 80 best chess players in the world) were carriers of the CC genotype (0 vs. 46.3%; OR = 16.4, p = 0.005). Furthermore, Russian and Tatar PhD holders had a significantly higher frequency of CT/TT genotypes compared with controls (meta-analysis: OR = 1.71, p = 0.009). Overall, this is the first study to provide comprehensive evidence that the rs17070145 C/T polymorphism of the KIBRA gene may be associated with ability in chess and science, with the T allele exerting a beneficial effect.

Background: Obesity is a global health issue influenced primarily by genetic variants and environmental factors. This study aimed to examine the relationship between genetic and lifestyle factors and their interaction with obesity risk among university students. Methods: A total of 658 students from the same university participated in this study, including 531 females (mean age (SD): 21.6 (3.9) years) and 127 males (21.9 (4.6) years). Among them, 550 were classified as normal weight or underweight (456 females and 94 males), while 108 were identified as overweight or obese (75 females and 33 males). All the participants underwent anthropometric and genetic screening and completed lifestyle and sleep quality questionnaires. Results: The polygenic risk score, based on seven genetic variants (ADCY3 rs11676272, CLOCK rs1801260, GPR61 rs41279738, FTO rs1421085, RP11-775H9.2 rs1296328, SLC22A3 rs9364554, and TFAP2B rs734597), explained 8.3% (p < 0.0001) of the variance in body mass index (BMI). On the other hand, lifestyle factors—such as meal frequency, frequency of overeating, nut consumption as a snack, eating without hunger, frequency of antibiotic use in the past year, symptoms of dysbiosis, years of physical activity, sleep duration, bedtime, ground coffee consumption frequency, and evening coffee consumption time—accounted for 7.8% (p < 0.0001) of the variance in BMI. The model based on gene–environment interactions contributed 15% (p < 0.0001) to BMI variance. Conclusions: This study revealed that individuals with a higher genetic predisposition, as defined by the seven polymorphic loci, are more susceptible to becoming overweight or obese under certain lifestyle conditions.

Interindividual differences are associated not only with body weight but also determine the body’s response to diet and physical activity. This systematic review aims to identify the genetic markers associated with diet-induced and exercise-induced weight loss. The eligible intervention studies for this systematic review contain all the necessary parameters for genetic polymorphism, diet, exercise, and changes in anthropometric or body composition parameters. In total, 91 articles meet the criteria and are included in this systematic review. The vast majority of studies (n = 88) use the candidate gene approach, and only three studies are performed using the hypothesis-free approach (Genome-wide association studies (GWAS)). A total of 98 genetic variants are found, of which 72 markers are associated with the efficiency of diet therapy, and 26—with individual response to physical activity. It should be noted that the significance of markers is replicated for only 10 of 98 genetic variants. In the near future, we should expect progress in this area, which will result in the development of a method for the individual selection for each patient of the type of diet and exercise for the prevention and treatment of obesity.

Introduction. ABC transporters (ATP-binding cassette transporters) are a class of membrane transporter proteins that play a crucial role in various physiological processes, including nutrient uptake, the secretion of signaling molecules, and the elimination of toxins. In addition to the above physiological functions, these proteins play a crucial role in the development of multidrug resistance in malignant neoplasms, thereby contributing to the progression of the disease. The main types of ABC transporters, for which their clinical significance in the development of drug resistance to chemotherapy and targeted therapy in many malignant neoplasms has been proven, include P-glycoprotein (P-gp, MDR1), BCRP and MRP1. However, the role of these proteins in the pathogenesis of gastrointestinal stromal tumors (GIST) and the formation of their resistance to chemotherapy is poorly understood. Aim. To assess the expression of ABC transporters (ABCB1/MDR1, ABCC1/MRP1, and ABCG2/BCRP), the intracellular content of their fluorescent substrates, and stemness markers in imatinib mesylate (IM) sensitive and resistant GIST cell lines, and their role in resistance to chemotherapy. Materials and methods. The study was conducted using GIST cell lines sensitive (GIST T-1) and resistant (GIST T-1R and GIST 430) to IM. As a positive control for the overexpression of ABC transporters in tumor cell lines, we utilized the previously obtained subline of triple-negative breast cancer HCC 1806 Tx-R, which has been proven to exhibit overexpression of ABC transporters. Results. We observed the increased expression of some ABC transporters (MRP1, ABCG2, and MDR1) in the IM-resistant GIST 430 cell line. This resulted in a significant increase in the excretion of their fluorescent substrate rhodamine 123 compared to the IM-resistant GIST T-1R cell line. At the same time, in the presence of P-gp inhibitors (cyclosporine A and tariquidar), as well as MRP1 (MK-571), there was a significant increase in the number of rhodamine-positive cells. A similar pattern was observed for some chemotherapeutic agents exhibiting autofluorescent activity, specifically an increase in the intensity of their fluorescence in the presence of corresponding ABC transporter inhibitors, indicating an increase in their intracellular concentration in GIST 430. Moreover, for doxorubicin, its excretion from GIST cells was proven exclusively by MRP1 protein, while mitoxantrone was “pumped out” from cells mainly through P-gp. The result of hyperexpression of these transporters in GIST 430 cells was their resistance to the drugs mentioned above, as evidenced by a 4- and 5-fold increase in the values of half-maximal inhibitory concentrations (IC50) for doxorubicin and mitoxantrone, respectively, in relation to GIST 430 cells compared to the GIST T-1R cell line. Based on the results of expression of stemness markers (CD44 and CD133) and colony formation, no evidence of the presence of a pool of cells with a stemness phenotype in the GIST 430 cell line was obtained. Conclusion. One of the mechanisms of secondary resistance of GIST 430 cells to chemotherapy is the hyperexpression of ABC transporters (MRP1, ABCG2, and MDR1), which is not associated with the presence of cells with a stemness phenotype in this cell line.