Adiposity is a condition of being severely overweight or obese and it has numerous connections to epigenetics. Understanding more about the epigenetics underlying obesity could help to introduce preventions based on lifestyle changes which may be able to modify our epigenetic marks and improve health.
A rough measure of obesity is body mass index, BMI, which can be calculated by dividing one’s body weight in kilogram by the body height in square meters. According to the World Health Organization (WHO) adiposity is characterized by a BMI over 30 kg/m². Adiposity is associated with several secondary diseases like type-2 diabetes, high blood pressure, cardiovascular diseases, fatty liver and disorders of the adipose tissue.
Epigenetics and obesity
Recent research has found that early epigenetic nutrition memory could program a person for obesity later in life and that a network of imprinted genes could act as a switch between lean and fat body types. This triggers a life-long, epigenetically-driven decision resulting in a stable phenotype of either lean or obese. Another study suggests that the metabolic consequences of mom and dad’s dietary habits can be inherited by their kids via epigenetic mechanisms, possibly setting them up for obesity or type 2 diabetes when they grow older.
While many past studies have implied that methylation marks due to perinatal exposure predispose people to obesity, Whal et al. (2017) suggest that some of the methylation marks are actually a consequence of an obese phenotype and not necessarily the cause. The team of researchers performed an epigenome-wide association study to show that body mass index is associated with widespread changes in DNA methylation.
The researchers found that 120 of the identified CpG sites show directional consistency for association with BMI in both adipose tissue and blood. Genetic association and causality analyses were then performed in order to determine if the identified methylation signals underlie the development of adiposity or are the consequence of adiposity. The results suggest that adiposity determines the alterations in methylation at the majority of the identified CpG sites. Therefore, the modification in DNA methylation was predominantly the consequence of adiposity rather than the cause.
The association of sentinel methylation markers with BMI was also analyzed in samples of the liver, and they found that the relationship between methylation and BMI in blood is also found in adipose and liver cells. The cross-tissue analysis represents the first step towards extending the observations found in blood to metabolically relevant tissue and its potential effect on metabolic pathways. Methylation risk scores were generated and used to predict type 2 diabetes beyond traditional risk factors, such as BMI and waist-hip ratio.
Lifestyle plays a role in epigenetic profiles and health
In the future, these scores may be used to identify obese and overweight individuals that are at increased risk of developing type II diabetes. It may also provide new insight into the biological pathways influenced by adiposity and may enable development of new strategies for prediction and prevention of type 2 diabetes.
The findings in this study suggest that the methylation changes in the blood may in part be a consequence of the changes in lipid and glucose metabolism associated with BMI. However, methylation marks are dynamic and can be adjusted with the right lifestyle changes. Interventions such as exercise, diets and weight loss surgery have been shown to modulate methylation marks in different tissue types.
In the Huang et al. (2015) study, normal weight individuals and successful weight loss maintainers displayed similar methylation patterns relative to obese individuals. This suggests that methylation marks can be modified by reduction in body weight and fat mass. This study is further confirmed by a previous study where the methylation profiles of obese individuals became more similar to those of lean individuals following weight loss surgery (Barres et al., 2013). Both these studies indicate how lifestyle changes can modify your epigenetic profile.
All of these studies suggest that your current BMI is strongly associated with your methylation profile. The results also indicate that several epigenetic marks are modifiable through lifestyle changes; therefore there is the potential for interventions to be introduced in order to modify unfavorable epigenomics marks.
The obesity epidemic threatens to reduce the length and quality of life of current and future generations. There are approximately 1.5 billion people worldwide are overweight or affected by obesity and are at risk of developing type 2 diabetes, cardiovascular disease and related metabolic and inflammatory disorders. These studies provide insight into the prediction and prevention of obesity and the diseases associated with adiposity.
Sources:
- Barres et al. Weight loss after gastric bypass surgery in human obesity remodels promoter methylation. Cell Rep, 2013. 3, p. 1020–1027.
- Huang et al. Epigenetic patterns in successful weight loss maintainers: a pilot study. International Journal of Obesity, 2015. 39, p 865-868.
- Van Dijk et al., Epigenetics and human obesity. International Journal of Obesity, 2015. 39, p. 85-97.
- Wahl et al., Epigenome-wide association study of body mass index, and the adverse outcome of adiposity. Nature, 2017. 541, p. 81-86.
