At the annual conference of the European Society of Human Genetics, an international group of researchers presented important findings about the link between obesity and the related diseases it causes.
Worldwide, the obesity epidemic continues to increase. In some developed countries, two-thirds of adults are either overweight or obese. Obesity is a dangerous disease that is known to increase the risk for stroke, heart disease, cancer, osteoarthritis, and other conditions.
An international team of researchers led by Taru Tukiainen from the Institute for Molecular Medicine Finland (FIMM) and colleagues from the U.S. and the United Kingdom investigated the association between body mass index (BMI) and gene expression in 44 distinct types of tissue, such as the brain and internal organs.
“Most tissue sampling is invasive, but we were able to use the GTEx dataset of tissues from autopsy donors, and therefore sample a far wider range than is usually possible,” Tukiainen explained in a news release.
“This is the first time that such changes in human tissue function in response to alterations in BMI have been explored among so many body systems simultaneously,” she added.
The investigators discovered concurrent alterations in response to obesity in almost all the tissues they examined.
“These results show that obesity really is a systemic condition, and particularly a condition of systemic inflammation. Interestingly, though, the changes in tissue function appeared to be only partially shared between different types of tissues; some tissues clearly act in pairs with one half of the pair compensating for — or enhancing — the dysfunction of the other,” Tukiainen said.
“For instance, adipose tissue and adrenal glands, which are both organs secreting hormones essential to metabolism, often react to changes in BMI in completely opposite ways, including a decrease in metabolic activity in the former and an increase in the latter,” she noted.
Lifestyle changes are the most efficient strategy against obesity, but these can be hard to maintain, so the biological mechanisms the researchers found may help the treatment of obesity by identifying potential drug targets. The study findings may also help to differentiate groups of individual at increased risk for developing health complications, and lead to tailored care in clinical practice.
“Our research highlights the burden of overweight and obesity on the digestive system. Although this is unsurprising, given the role of digestive system tissues in food processing, we found alarming links between BMI-related changes in different parts of the digestive tract and genes implicated in some diseases, for example Crohn’s disease,” Tukiainen said.
“An association between two variables does not necessarily imply there is a causal link and, from the gene expression results alone, we cannot tell which is driving which. Do changes in BMI or changes in gene expression come first? We can, however, address the potential causes by using genetic variants known to be associated with BMI in combination with our data on gene expression,” she added.
Studies have already identified almost 100 genetic variants that have an impact on BMI. Many of these changes in gene variants, especially in adipose tissue, seem to be caused by an increased BMI.
“I believe that our work adds to the weight of evidence, and provides hypotheses for other researchers to follow up in the hope of being able to translate the results into ways of preventing and treating the very serious complications of obesity,” Tukiainen concluded.
