Scientists have finally worked out why obese people get organ failure far from where they carry their extra pounds – because body tissue is linked by type, not location.
Doctors say it has been difficult to understand the havoc carrying extra pounds wreaks on our insides until, but they hope the discovery will lead to better personalised treatment for those at risk of obesity.
A new analysis has revealed the links between body mass index (BMI) and genes in 44 different types of tissue – such as the brain – to show exactly what being overweight does to the organs, bones and muscles.
Although lifestyle changes are the most effective way to combat obesity, they can be hard work and difficult to maintain, so the biological processes identified may help develop potential drugs for particular tissues.
The results may also help distinguish groups of individuals who are at higher risk of developing complications, and lead toward personalised care.
Taru Tukiainen, a postdoctoral researcher at the Institute for Molecular Medicine Finland, Helsinki, said: “This is the first time such changes in human tissue function in response to alterations in BMI have been explored among so many body systems simultaneously.”
Her researchers found changes in response to obesity in almost all the tissues studied.
Dr Tukiainen told the European Society of Human Genetics annual meeting in Barcelona: “These results show 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.
“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.”
The study used a dataset known as GTEx which consists of thousands of tissue samples in which bits of DNA called RNA has been sequenced to measure gene expression.
Because it is not collected specifically for obesity research it is representative of the population as a whole, and the obesity epidemic is reflected in that only 31% of GTEx donors are or normal weight; the remainder are either overweight or obese.
Obesity is on the rise throughout the world, and in some developed countries two-third of the adult population is either overweight or obese, leading to rises in patients with serious conditions such as heart disease, stroke, cancer and osteoarthritis.
Many of these conditions do not appear to affect the parts of the body where the excess fat accumulates, but rather to involve body systems that are more remote.
Dr Tukiainen said: “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.
“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.
“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.”
Large scale DNA studies have already identified almost 100 mutations that influence BMI. Analyses by the group that interpret this information further have shown that many of these gene expression changes, particularly in adipose tissue, appear to be caused by increased BMI.
Dr Tukiainen added: “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,”
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