🧬 Why do some people not lose weight on low-calorie diets? The answer lies in the genes

Many people believe that reducing calorie intake and exercising more is enough to lose weight. However, practice and science show that the same diet regimen does not produce the same results for everyone. While some lose weight easily, others — despite discipline and calorie reduction — barely notice the change. The latest research in the field of nutrigenetics reveals that one of the reasons for this is the genetics of obesity .

🔹 Perilipin (PLIN) gene - resistance to fat loss

Studies conducted by José Ordovás and colleagues indicate that certain variants of the PLIN gene , which regulates fat storage in cells, can significantly reduce the effectiveness of low-calorie diets. In people who carry this genetic polymorphism, energy storage mechanisms are more stable and resistant to calorie restriction. The result?

Less weight loss even with good adherence to the diet.

In other words, the body of these people "defends itself" against fat loss - it conserves energy reserves and slows down the metabolism.

🔹 CB2R gene - influence on energy balance and inflammation

CB2R gene variants (especially the A allele of rs3123554) are associated with less weight loss and more modest metabolic improvements during low-calorie diets. The CB2R receptor affects energy balance, inflammation, and insulin sensitivity , which means that genetic differences in this pathway can alter the way the body responds to calorie restriction.

🔹 APOA5 gene - differences in fat metabolism

Another important gene is APOA5 (rs662799) , which plays a key role in triglyceride metabolism . In people with the C allele, smaller improvements in triglyceride levels, insulin and insulin resistance (HOMA-IR) were noted during the Mediterranean low-calorie diet — although all subjects lost weight. Thus, the genetic background does not only affect how much weight we lose , but also the quality of the metabolic changes that the diet causes.

🔹 What does this mean for practice?

These findings confirm that low-calorie diets are not equally effective for everyone . For people with the mentioned genetic variants, weight loss success may require a different approach - a more precise balance of macronutrients, a higher intake of protein and fiber, a focus on the quality of fats, as well as the inclusion of supplements and physical activity adapted to genetics.

Genetic differences in the PLIN, CB2R, and APOA5 genes explain why "one diet fits all" doesn't work.

Thanks to tests in the field of nutrigenetics , today we can adapt nutrition to the genetic profile and thus achieve better and more lasting results.

Also read: How genes affect obesity