There’s no doubt that obesity is a public health menace; in some developed countries about two-thirds of the adult population is overweight or obese. Despite overwhelming evidence that obesity is a main contributor to several serious health conditions, the obesity epidemic shows no signs of slowing down, and many people choose to partake in a lifestyle that puts them at risk.

Many of the ailments associated with obesity have nothing to do with the body parts where fat accumulates, however, prompting a reasonable question: How does obesity cause disease in organs and tissues where fat won’t deposit? An international team of researchers has just taken a huge step toward a true understanding of this relationship between obesity and physically distant diseases.

Dr. Taru Tukiainen, of the Institute for Molecular Medicine Finland, and her colleagues from the United Kingdom and United States, took a look at the relationship between body mass index (BMI) and gene expression in 44 different tissue types. Some of these genes, including those from the brain and internal organs, are rarely accessible in large amounts.

“Most tissue sampling is invasive, but we were able to use [a] dataset of tissues from autopsy donors, and therefore sample a far wider range than is usually possible,” Tukiainen said in a press 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.”

The team observed simultaneous, obesity-related changes in almost all of the tissues they looked at. Tukiainen said the results show obesity truly is a systemic condition, causing inflammation in particular. She did point out, however, that changes in tissue function appeared to be only partially shared between different types of tissues.

“Some tissues clearly act in pairs with one half compensating for — or enhancing — the dysfunction of the other,” she 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.”

Identifying which biological processes contribute to obesity-related disease may help researchers find potential targets for drug treatment. Though lifestyle changes are the most effective way to combat the condition, they can be difficult to maintain. In addition, the results may help clinicians identify which individuals are at high risk of developing complications of obesity, leading to more personalized care.

“Our research highlights the burden of overweight and obesity on the digestive system,” Tukiainen said. “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 cautioned that an association between the two does not necessarily imply a causal link, and the researchers were unable to determine which variable is driving which. Other researchers will need to follow up on the results, but Tukianen said she hopes the findings can lead to a way to prevent and treat the complications of obesity.

Source: Tukiainen T, et al. Multi-tissue Transcriptome Analysis Reveals Disease-Relevant and Causal Links Between Obesity and Gene Expression. European Society of Human Genetics Conference. 2016.

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