A recent study identified 14 genes linked to improved weight loss when combined with moderate exercise, such as running for 30 minutes three times a week. The PARGC1A gene alone contributed to 62% of the weight loss in participants. Participants with the highest number of these “skinny genes” lost up to 5kg in eight weeks, while others lost around 2kg. The PARGC1A gene alone contributed to 62% of the weight loss in participants. This research supports the need for a balanced approach, combining genetics with exercise and diet for best results.
For decades, the rise in obesity and unhealthy weight has been a growing challenge, impacting both public health and the economy. In the UK, for example, around 64% of adults are overweight or obese, conditions that increase the risk of heart disease, type 2 diabetes, and premature death.
Losing weight, even just 5% of body weight, can have major health benefits, such as improving metabolic indicators and reducing the risks associated with obesity. Therefore, medical guidelines recommend that overweight people actively seek to reduce their weight. Physical activity (PA) plays an important role in this reduction, helping not only with weight loss but also in mitigating the negative effects of obesity, such as cardiovascular problems.
However, many people face difficulties in engaging in regular exercise, whether due to lack of access to gyms, lack of time, or other factors. Even so, many activities can be done at home or in public spaces, such as running outdoors. Despite the well-documented benefits of PA, many people still find it difficult to lose weight in a lasting way.
Weight loss occurs when the body uses more energy than it consumes, either by eating less or exercising more. In addition, PA has health benefits that go beyond the scale. Higher levels of physical fitness are linked to lower mortality and better metabolic health, regardless of weight.
Studies show that even moderate exercise can result in modest weight loss (about 2 to 3 kg) over a few weeks or months. In addition, exercise helps reduce visceral fat (around the organs) and preserves muscle mass during weight loss.
However, responses to exercise vary greatly between people. While some lose a lot of weight, others see little change, even following the same exercise regimen. This factor can be influenced by each individual’s genetics. Genetic factors affect not only appetite and metabolism, but also how the body responds to physical activity.
A recent study, led by researchers at the University of Essex, investigated how different genetic profiles might affect weight loss after an 8-week exercise program. In the study, one group of 17 people participated in a running program, while another group of 21 participants did no exercise; the participants ranged in age from 20 to 40 years old. The participants’ diets were not changed, only their exercise regimen was manipulated to isolate the effects.
The exercise group completed a periodized running program consisting of 20 to 30 minutes of walking, on an agreed route, three times a week, while the control groups abstained from daily exercise. Participants were screened at the end of the study for 1,000 genetic variants using a DNA testing kit.
In the end, the participants who ran lost weight, but the amount varied greatly. Genetic analysis revealed that certain genetic variations, known as SNPs (single nucleotide polymorphisms), were associated with greater weight loss. Individuals with these genetic variants lost up to 5 kg, while those without these variants lost an average of 2 kg.
The PARGC1A gene, in particular, which encodes PGC-1-a, has been identified as crucial to weight loss. PPARGC1A interacts with a wide range of transcription factors that modulate energy expenditure, fat burning, weight control and obesity. The researchers found that 62% of the variation in weight loss was related to genes, while the other 38% was linked to physical activity and lifestyle.
Despite this finding, Dr. Henry Chung, who led the study, emphasized that genetics alone are not enough: genes need to be combined with exercise and lifestyle changes to achieve the best results.
In addition to PARGC1A, the researchers identified 13 other genes that were also associated with weight loss. Interestingly, the SNPs identified in this study fell into two distinct groups:
Those associated with genes (PPARGC1A; COL1A; CPT1B; BDNF; HCP5; SOD2; FGF5; SMAD3; TBX3) involved in the control of diet, adiposity, and/or energy metabolism
Those associated with genes (CHRNA5; VRK2; LIN28B; TDRD9; POU3F2) involved in intelligence and/or psychological conditions, particularly depressive illnesses
The table shows the alphabetical list of genes associated with reductions in BMI.
In summary, these were all the genes:
PPARGC1A (PGC-1α): This gene regulates energy metabolism, controlling processes such as mitochondrial biogenesis (production of mitochondria), carbohydrate and lipid metabolism, and the development of muscle fibers. It is associated with conditions such as obesity and diabetes.
SMAD3: This gene acts in the regulation of glucose and lipids, being an important factor in mitochondrial biogenesis in fat cells. It also represses the expression of PPARGC1A, influencing how the body responds to exercise.
HCP5: This is a non-coding RNA (LncRNA) that promotes the formation of fat cells and increases the oxidation of fatty acids.
CPT1B: This gene is crucial for the transport of fatty acids to the mitochondria, where they are used as energy, which can influence the success of exercise programs focused on burning fat.
BDNF: Associated with appetite control and body weight. Variations in this gene have been linked to obesity, suggesting that decreased BDNF activity may lead to weight gain regardless of exercise levels.
SOD2: This gene protects cells from oxidative stress. People with certain SOD2 variants tend to have a significant reduction in body mass index (BMI) in response to exercise programs, suggesting that antioxidant activity may influence weight control.
FGF5: Associated with adiposity (fat accumulation) and high blood pressure, FGF5 is also linked to obesity risk. Variations in this gene may influence how the body stores fat and responds to metabolic risk factors.
TBX3: This gene is involved in sensing and controlling energy status in the brain. Deficiencies in TBX3 have been associated with obesity, and it is thought to be an important factor in the development of neurons that regulate appetite and weight control.
COL1A1: Although primarily involved in collagen formation, this gene has also been associated with increased body mass in studies investigating muscle injury, suggesting a possible connection with body composition and energy metabolism.
CHRNA5: This gene is related to smoking behavior, affecting body weight control. Nicotine, by influencing appetite, can reduce body mass index (BMI) in smokers. Variations have been associated with reduced BMI in smokers, and greater ease in quitting smoking, especially in individuals without depression.
VRK2: Variations in this gene have been strongly associated with psychiatric disorders, such as major depression. The SNP showed a significant correlation with depression and also with obesity, suggesting a genetic link between the risk of depression and body weight regulation.
LIN28B: This gene is involved in development and growth, and is also associated with major depression.
TDRD9: This gene has a strong genetic overlap with depression and changes in body mass. Upregulation of the TDRD9 gene is linked to obesity and type 2 diabetes.
POU3F2: Variations in this gene are associated with intelligence and educational level. This correlates with a lower likelihood of obesity in individuals with high intelligence. This suggests that genetic factors that influence cognition may also affect lifestyle choices, such as diet and exercise.
This study highlights the importance of personalized approaches to weight loss, taking into account both genetic and lifestyle factors. This may pave the way for more effective and individualized treatments in the future.
READ MORE:
Genotypic Variations Associated with Changes in Body Mass in Response to Endurance Training
Henry C. Chung, Don R. Keiller, Sally P. Waterworth, Chris J. McManus, Justin D. Roberts & Dan A. Gordon
Abstract:
This study investigates the extent to which different genotypes can explain changes in body mass following an 8-week running program, in a UK population. Participants were randomly assigned to either a training (n = 17) or a control group (n = 21). Participants’ diets were not altered, only the exercise regime was manipulated to isolate effects. The exercise group completed a periodized running program consisting of 20–30 min, over an agreed route, three times per week, whilst the control groups refrained from daily exercise. Participants were screened at the end of the study for 1,000 gene variants using a DNA test kit. Results demonstrated a significant reduction in body mass, within the exercise, compared to the control group (p = .002). This reduction in body mass varied significantly (p = .024) between individuals within the exercise group. Moreover, genetic analysis identified 17 single nucleotide polymorphisms (SNPs) associated with this variation (r2 = .74; p < .001). These findings indicate that individuals with specific alleles are better predisposed to weight management, compared to their counterparts, following an exercise program. This study helps to bridge the gap between population health and exercise science and can inform research in the application of genetics to help develop individually tailored health interventions.
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