Nature vs. nurture: What fuels obesity, diabetes?

Yella Hewings-Martin PhD
Add to MyMedicalExpo favorites

Our environment and lifestyle can affect the function of our genes without altering the genetic code. A review article summarizes research over the past decade showing how this contributes to obesity and type 2 diabetes.

Nature versus nurture is a phrase with which many of us are familiar. Our genes are responsible for many of our traits, but nurture or environmental influences surely have a part to play.

When it comes to obesity and type 2 diabetes, it is easy to follow a straightforward train of thought.

If we consistently consume more calories than we burn each day, we put on weight, and this predisposes us to develop type 2 diabetes.

Our fat cells and pancreas recover once we change our lifestyle and lose weight. However, this simple equation leaves us with many unanswered questions.

Why do some people lose weight more quickly than others, even if they follow the same diet or exercise regimen? Why do some people develop type 2 diabetes while others do not, even when their genetic risk is similar?

Epigenetics may hold the answers to some of these questions. A relatively young branch of genetics, epigenetics is the study of changes in gene function without any alterations to the genetic code, or genome, itself.

Can epigenetics explain the rising rates of obesity and type 2 diabetes?

Epigenomes are individual and dynamic

Epigenetic modifications are one way to influence how a gene functions.

DNA methylation is one type of epigenetic modification. It occurs when small chemical tags called methyl groups attach to cytosine bases in the DNA code. This methylation switches a gene off.

We inherit some epigenetic markers from our parents, but many occur spontaneously and change during our lifetime, fashioning each of us with a unique epigenome.

In an article in the journal Cell Metabolism, researchers from Lund University in Sweden recently reviewed studies with human participants that investigated how DNA methylation contributes to obesity and type 2 diabetes.

Charlotte Ling, a professor at the Lund University Diabetes Center, explains in a press release that "epigenetics is still a relatively new research field; however, we now know that epigenetic mechanisms play an important role in disease development."

In the paper, Ling explains that researchers have found a number of epigenetic modifications throughout the genome that could predict the body mass index of a person to some degree.

When comparing the DNA methylation sites in pancreatic islets — the structures that produce insulin — from people with type 2 diabetes and those without the condition, one study identified nearly 26,000 regions that were different between the two groups.

Lind advises caution though, as it is unclear at this point whether these changes are the cause or effect of type 2 diabetes.

powered by Rubicon Project

Diet, exercise, and aging

There is plenty of evidence linking obesity and diabetes with Western diets containing high levels of fat and sugar.

Epigenetic studies may tell us why.

"A 5-day high-fat diet overfeeding, mimicking the diet seen in many obese people, changed both the gene expression and methylation patterns in human skeletal muscle and adipose tissue," explains Ling.

"Importantly, it seemed easier to induce methylation changes by overfeeding than to reverse them by a control diet," she continues.

Exercise also affects the epigenome. Both single sessions and long-term exercise changed DNA methylation in skeletal muscle and fat, but the gene targets were different.

"Epigenetics can explain why different people respond differently to exercise," comments Tina Rönn, study author and a postdoctoral researcher working with Ling.

As we age, our epigenome continues to alter, pointing the finger at aging as a driving factor in epigenetic changes. Research links obesity with epigenetic drift as a person ages, but how or why this happens is unclear at the moment.

What happens to the next generation?

Studies in rodents show that one generation can pass some epigenetic markers associated with obesity and type 2 diabetes to the next generation. In humans, this type of research is in its infancy, but some interesting results are emerging.

In one study, children of mothers who had type 2 diabetes during pregnancy had a higher risk of developing obesity and type 2 diabetes in later life than children of mothers without diabetes.

Several studies show that when mothers experience famine during pregnancy, their children are at increased risk of obesity and glucose intolerance, possibly due to changes in the methylation of the leptin gene.

Yet, it is not just mothers who leave their mark in the next generation's epigenome. Sperm from obese men has unique DNA methylation patterns, which change after bariatric surgery.

What does this mean for our health?

Ling and Rönn suggest using DNA methylation at known risk sites in the genome as biomarkers to help identify those individuals at higher risk of developing obesity and type 2 diabetes.

With the help of better biomarkers, it may be possible to show DNA methylation sites that are significant risk factors and then use pharmacological agents to change the methylation pattern.

Such epigenetic drugs do, in fact, already exist, and scientists have tested them in other conditions, such as certain types of leukemia.

A recent study showed that treatment with a type of epigenetic drug, a histone deacetylase inhibitor called MC1568, improved insulin secretion in pancreatic islets that people with type 2 diabetes donated.

"The transient and reversible nature of epigenetic modifications provides an open field for discovery of targets for future prediction and therapeutic concepts in obesity and [type 2 diabetes]."

Charlotte Ling and Tina Rönn

It is important to remember that DNA methylation is only one type of epigenetic modification. With the research field slowly emerging from its infancy, there are bound to be some interesting discoveries on the horizon.

It remains to be seen whether they will settle the debate once and for all on nature versus nurture in obesity and type 2 diabetes.

Does lifestyle affect how our genes behave?
 

Does lifestyle affect how our genes behave?