Low-Cal Diet Could Change Epigenetic Patterns in Obesity-Related Disease

Obesity is a disease characterized by excessive body fat. It can be caused by environment, a person’s early-life nutrition, and it can even be a result of their parent’s diet. Obesity is so dangerous because associated with many diseases such as hypertension, type-2 Diabetes, cardiovascular disease, and cancer. How does extra weight cause so many different problems? Many studies point to the fact that these diseases are, at least partially, mediated by epigenetics.

In a study published in the European Journal of Clinical Nutrition, researchers from the University of Sao Paulo looked at DNA methylation patterns in obese women versus women with BMI in the normal range, and how these patterns could affect health outcomes.

DNA methylation is an epigenetic mechanism that occurs when a methyl group is added to the cytosine group on DNA. This addition alters gene expression, often resulting in gene silencing.

The team found that women with normal BMI had on average around 11% more methylation marks on their DNA. They wanted to see whether weight loss by a short term low-calorie diet would restore the DNA methylation levels in obese women to the level of women with normal BMI.

The obese women (with an average BMI of 58.5 at the start of the experiment) went on a controlled low-calorie diet for 6 weeks, where they ate merely 1200 calories a day. Along with losing weight, their DNA methylation profiles changed drastically.

At the end of the experiment, there was a change in DNA methylation at more than 16,000 sites around the genome associated with more than 9,200 genes. Many of the implicated genes were linked to epigenetic pathways of cancer.

Conversely, despite the low-calorie diet, there were methylation sites associated with around 650 genes that did not change with the dietary intervention and remained different between obese and normal-weight women. The epigenetically beneficial effect of the diet was thus, only partial. Future studies are needed to discover whether a longer-term diet or a one where the healthy weight is achieved is able to fully restore the epigenetic effects of obesity.

Caloric restriction has been studied in animals for decades for its proposed beneficial effects. In rats, it has been shown to increase lifespan. Human studies from Blue Zones – places on Earth where people live unusually long lives – also point to the fact that low-calorie diets are good for us.

For example, the inhabitants of Okinawa, Japan who are known to eat low-calorie diets have exceptionally long lifespans and very low incidence of disease. While the reasons behind the benefits of caloric restriction are likely complex, the present study points to epigenetics as the potential link between improved health and longevity.

While caloric restriction should be exercised with caution, the results of the study are promising. They highlight the link between weight loss by low-calorie diets and epigenetic changes associated with better health outcomes. It shows that with the right intervention, unhealthy states linked to obesity can be at least partially reversed.


Nicoletti, C.F. et al. (2020) DNA methylation pattern changes following a short-term hypocaloric diet in women with obesity. Eur J Clin Nutr.  


Crujeiras, A.B. et al. (2019). Identification of an episignature of human colorectal cancer associated with obesity by genome-wide DNA methylation analysis. Int J Obes. 43:176–88.

Simons, M.J. (2013). Dietary restriction of rodents decreases aging rate without affecting initial mortality rate – a meta-analysis. Aging Cell. 12:410–4.

Willcox, B.J. et al. (2007). Caloric restriction, the traditional Okinawan diet, and healthy aging: the diet of the world’s longest-lived people and its potential impact on morbidity and life span. Ann N Y Acad Sci. 2007;1114:434-455.

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About Fanni Daniella Szakal 2 Articles
Fanni got her BSc in Genetics from the University of Edinburgh and continued on to an MSc in Marine Biology at the University of Amsterdam. After some years of research covering many organisms from yeast to dolphins, she decided to turn towards communicating science. She is fascinated by epigenetics, the magic link between genetics and the environment. In her free time, she travels when she can, hiking in the mountains and climbing as many rocks as possible.

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