Scientists discovered that people respond differently to dieting because of differences in their genes. When researchers looked at blood cells from people who lost a lot of weight versus those who lost less weight on the same diet, they found major differences in which genes were turned on and off. The biggest difference involved genes that control how flexible and stretchy your body’s tissues are. People who didn’t lose as much weight had genes that made their tissues stiffer and less flexible. This discovery helps explain why the same diet works better for some people than others, and could eventually help doctors create personalized weight loss plans.

The Quick Take

  • What they studied: Why some people lose much more weight on a calorie-restricted diet than others, by looking at which genes are active in their blood cells
  • Who participated: People who followed the same calorie-restricted diet but had very different weight loss results—some lost much more weight (hyper-responders) and some lost much less (hypo-responders)
  • Key finding: People who lost less weight had 1,581 genes that worked differently in their blood cells compared to people who lost more weight. The biggest difference involved genes that control how stretchy and flexible body tissues are. People who lost less weight had stiffer tissues, which may make it harder to lose weight.
  • What it means for you: Your genes may play a big role in how well you respond to dieting. This suggests that a one-size-fits-all diet approach may not work for everyone, and personalized diets based on your genes might be more effective in the future. However, this is early research and more studies are needed before doctors can use this information to create custom diet plans.

The Research Details

Researchers put people on a diet where they ate fewer calories than normal. They measured how much weight everyone lost and divided them into two groups: people who lost a lot of weight (hyper-responders) and people who lost less weight (hypo-responders). Then they took blood samples from both groups and looked at which genes were turned on and off in their blood cells. By comparing the gene activity between the two groups, they could identify which genes might explain why some people lose more weight than others.

This type of study is called a transcriptomic analysis, which means scientists looked at which genes were active (turned on) versus inactive (turned off) in the cells. It’s like looking at a control panel to see which switches are flipped in each person’s body.

Understanding the genetic differences between people who respond well to diets and those who don’t is important because it could help doctors create better, personalized weight loss plans. Instead of giving everyone the same diet advice, doctors could eventually test someone’s genes and recommend a diet that’s more likely to work for them specifically. This research approach helps identify the biological reasons why diets work differently for different people.

The researchers used strict statistical methods to identify real differences in gene activity (they used something called FDR ≤0.03, which means they were very confident the differences weren’t just by chance). They also used advanced computer analysis to look at how genes work together in networks. However, the study doesn’t specify exactly how many people participated, which makes it harder to judge how reliable the results are. The findings are interesting but are considered preliminary—they need to be confirmed by other researchers before they can be used in real medical practice.

What the Results Show

Both groups of people lost weight on the diet, but the hyper-responders (people who lost a lot) lost significantly more: 82% more total weight, 81.5% more in BMI (a measure of body size), 69% more in hip circumference, and 48% more in waist circumference compared to the hypo-responders (people who lost less).

When scientists looked at gene activity in blood cells, they found huge differences. Out of 1,581 genes that were different between the two groups, only one gene (called GSPT1) was more active in people who lost less weight. All the other 1,580 genes were less active in people who lost less weight.

The most important finding involved genes that control collagen, which is a protein that gives your body tissues their structure and flexibility. People who lost less weight had much lower activity in collagen-related genes. This suggests their body tissues were stiffer and less flexible, similar to what happens in people with obesity-related problems like insulin resistance (when the body has trouble controlling blood sugar).

The researchers found that the genes that were different between the two groups work together in specific pathways (like assembly lines in a factory). The most important pathway involved collagen production and how collagen is modified in the body. This pathway was significantly disrupted in people who lost less weight. The upregulation of the GSPT1 gene in people who lost less weight suggests their body may be in a different metabolic state—possibly with more inflammation or altered energy processing—that makes weight loss harder.

Previous research has shown that obesity is associated with stiffer tissues and problems with insulin resistance. This study adds new information by showing that people who don’t respond well to diets may have genetic differences that make their tissues naturally stiffer. This connects the genetic level (which genes are active) to the physical level (how flexible tissues are) and helps explain why some people have a harder time losing weight. The finding about GSPT1 is novel and suggests that inflammation and metabolic changes may be part of why some people resist weight loss.

The study doesn’t clearly state how many people participated, which makes it hard to know how reliable the results are. The researchers only looked at blood cells, not other tissues in the body, so we don’t know if the same gene differences exist in fat tissue or muscle. The study is observational, meaning researchers watched what happened naturally rather than randomly assigning people to different diets, so we can’t be completely sure the genes caused the different weight loss responses. Finally, this is early research, and the findings need to be confirmed by other scientists before they can be used to help patients.

The Bottom Line

Based on this research, there is moderate evidence that genetic differences affect how well people respond to calorie-restricted diets. However, this is preliminary research, and it’s too early to recommend genetic testing for weight loss planning. The current best approach is still to follow standard healthy eating advice: eat fewer calories than you burn, eat whole foods, exercise regularly, and get enough sleep. If you’re struggling to lose weight despite following these guidelines, talk to your doctor—there may be medical reasons (like thyroid problems or other conditions) that need to be addressed.

This research is most relevant to people who have tried multiple diets without success and want to understand why. It’s also important for doctors and researchers who develop weight loss treatments. People with obesity or metabolic problems should be aware that their genes may influence their weight loss response. However, this doesn’t mean genes determine your fate—lifestyle changes still matter, but they may need to be personalized based on your individual biology.

If personalized genetic testing for weight loss becomes available in the future, benefits would likely appear on the same timeline as regular dieting—usually a few weeks to a few months for noticeable changes. However, this research is still in the early stages, and it may take 5-10 years before genetic testing becomes a standard tool for weight loss planning.

Want to Apply This Research?

  • Track weekly weight, waist circumference, and hip circumference measurements alongside calorie intake and exercise. This allows users to see their personal response pattern to dieting and identify whether they’re a hyper-responder or hypo-responder, which can help adjust expectations and strategies.
  • Users who discover they’re hypo-responders (losing weight more slowly) should focus on consistency rather than expecting rapid results. The app could provide modified goals, celebrate non-scale victories (like improved energy or better sleep), and suggest consulting a healthcare provider about personalized approaches rather than standard diet plans.
  • Implement a 12-week tracking period with weekly measurements and monthly progress reviews. Compare individual response rates to average expectations. For users showing slower responses, the app could recommend medical evaluation to rule out metabolic conditions and suggest working with a nutritionist for personalized meal planning rather than generic diet advice.

This research is preliminary and has not yet been confirmed by other independent studies. The findings about gene expression differences are interesting but cannot yet be used to predict individual weight loss responses or to create personalized diets. If you’re struggling to lose weight, consult with a healthcare provider or registered dietitian before making major dietary changes. This information is for educational purposes only and should not replace professional medical advice. Genetic testing for weight loss is not yet a standard medical practice, and the clinical applications of this research are still being developed.