Have you ever thought, “If I just exercised a little more, I could lose that extra 20 pounds!”
A new study published in September 2024 looked at the relationship between weight loss, aerobic exercise, and genetics. It attempts to answer the question, “Who loses weight and why?
Losers and gainers:
Studies of exercise for weight loss show mixed results. For some people, exercise is a great way to lose weight, but for others, it doesn’t seem to have much of an effect. When you look at the results of studies on exercise and weight loss, most show a modest positive benefit. But what is hidden in these results is that some people lose a lot of weight with exercise, and others gain a little. The average weight of all study participants usually shows a decrease, but genetic variants probably play a role in who loses a lot of weight compared to the few who gain a little.
Previous studies show that aerobic exercise usually produces modest weight loss, on average for the group of participants. Here are a couple of examples:
- A study of one hour of aerobic exercise 3-5 days/week showed a weight loss of 1 kg compared to a control group after 12 weeks. While a few pounds of weight loss after three months of running or walking doesn’t sound like much, the participants actually lost a little more fat than the 1 kg and gained a little muscle mass.[ref]
- Another study involving women in a 12-week aerobic exercise program found that about three-quarters of the participants lost fat mass and one-quarter of the group gained a little. This study also showed a genetic link to who was likely to lose weight.[ref]
This new study tries to tease out which genetic variants are likely to accelerate weight loss with consistent, moderate aerobic exercise. The study involved two groups: a control group that avoided exercise and an active arm that ran for 20 to 30 minutes three times a week. They used a panel of 1,000 gene variants to see if there was a statistically significant association between genetic variants and the amount of weight loss. The results showed that a combination of genetic variants likely influenced weight loss with exercise.
The researchers highlighted the results for PPARGC1A, which encodes the PGC-1-a protein which is a transcriptional coactivator that modulates the amount of fat utilized for energy. Other studies also have found that PPARGC1A is involved in susceptibility to obesity. BDNF is another gene that multiple studies have linked to increased weight.
All together, the genes fall into two distinct groups. One group, which includes BDNF and PPARGC1A, is involved in the control of energy metabolism. The other group, which involved POU3F2, is linked to psychological conditions.
Related articles: PPARG and weight & BDNF for weight loss
Genotype report:
Participants who had more than half of the variants below (highlighted in yellow or orange) were more likely to lose weight with aerobic exercise.[ref]
| Gene | RS ID | Effect Allele | Your Genotype | Notes About Effect Allele |
|---|---|---|---|---|
| BDNF | rs4923460 | G | -- | Associated with decreased BMI with aerobic exercise (combined with other variants) |
| BDNF | rs6265 | C | -- | Associated with decreased BMI with aerobic exercise (combined with other variants) |
| CHRNA5 | rs16969968 | A | -- | Associated with decreased BMI with aerobic exercise (combined with other variants) |
| COL1A1 | rs1800012 | A | -- | Associated with decreased BMI with aerobic exercise (combined with other variants) |
| CPT1B | rs5770917 | T | -- | Associated with decreased BMI with aerobic exercise (combined with other variants) |
| FGF5 | rs16998073 | T | -- | Associated with decreased BMI with aerobic exercise (combined with other variants) |
| POU3F2 | rs12206087 | G | -- | Associated with decreased BMI with aerobic exercise (combined with other variants) |
| PPARGC1A | rs3774923 | C | -- | Associated with decreased BMI with aerobic exercise (combined with other variants) |
| PPARGC1A | rs10028665 | T | -- | Associated with decreased BMI with aerobic exercise (combined with other variants) |
| SMAD3 | rs17228058 | G | -- | Associated with decreased BMI with aerobic exercise (combined with other variants) |
| TBX3 | rs2384550 | A | -- | Associated with decreased BMI with aerobic exercise (combined with other variants) |
| TDRD9 | rs10149470 | G | -- | Associated with decreased BMI with aerobic exercise (combined with other variants) |
Lifehacks:
If more than half the variants are highlighted:
If you have a lot of highlights above, aerobic exercises may be helpful if you are trying to lose weight. The study participants did 20 to 30 minutes of jogging three days a week. Other forms of moderate aerobic exercise could include brisk walking, playing pickleball, hiking uphill, skiing, etc.
Only a few of the variants are highlighted:
If you don’t have a lot of variants highlighted in the genotype report, you may find that exercise alone doesn’t work well for you for weight loss. Instead, you may need to focus more on diet and circadian timing of food intake.
Other genetic interactions with weight loss:
Here are some of the other weight loss and genetics articles to check out:
The FTO gene was one of the first that was strongly identified by researchers as impacting weight. It turns on genes involved in fat storage, and it is also important in regulating appetite and muscle formation.
If you have the variants below, read through the full article for several options for more effective weight loss.
| Gene | RS ID | Effect Allele | Your Genotype | Notes About Effect Allele |
|---|---|---|---|---|
| FTO | rs9939609 | A | -- | Increased risk of obesity; higher BMI |
| FTO | rs1558902 | A | -- | Increased risk of obesity; higher BMI |
| FTO | rs3751812 | T | -- | Increased risk of obesity; higher BMI |
If you are considering taking a GLP-1 receptor agonist, such as semaglutide, this article covers the pathways involved and genetic variants that may impact weight loss results.
| Gene | RS ID | Effect Allele | Your Genotype | Notes About Effect Allele |
|---|---|---|---|---|
| GLP1R | rs6923761 | A | -- | better response to GLP1 receptor agonist for weight loss |
| GLP1R | rs10305492 | A | -- | less response to GLP1 receptor agonist for weight loss |
| TCF7L2 | rs7903146 | T | -- | less response to GLP1 receptor agonist for weight loss |
| CNR1 | rs1049353 | T | -- | improvement in insulin resistance along with weigh loss in GLP-1 receptor agonist |
UCP1 and Brown Fat: Turning up the heat
UCP1 is important in basal metabolic rate and the utilization of fat for producing heat. Genetic variants here may help you understand how to turn up the heat on energy production and weight loss.
| Gene | RS ID | Effect Allele | Your Genotype | Notes About Effect Allele |
|---|---|---|---|---|
| UCP1 | rs1800592 | C | -- | Increased risk for abdominal fat |
| UCP1 | rs6536991 | C | -- | Decreased risk of obesity |
| UCP1 | rs3811787 | G | -- | Increased risk of abdominal fat |