Why obesity causes metabolic problems

Scientists have made a new discovery about the nature of metabolic complications associated with obesity, such as type 2 diabetes. The findings could contribute to better treatments or preventative measures for metabolic complications, including type 2 diabetes.
Previous research has established that metabolic complications associated with obesity are caused by inflammation. When there is excessive weight gain, the adipose tissue develops abnormally, and therefore produces more “triggers” for inflammation. This can have negative consequences for the metabolism, including an increased risk of type 2 diabetes.
But this does not affect all obese people. In fact, when the adipose tissue expansion occurs somewhere superficial – in the subcutaneous regio, for example – the individual is less likely to develop metabolic complications. For a while, scientists had no idea why.
Then a previous study suggested that a transcription factor called Interferon Regulatory Factor 5 (IRF5) might have something to do with it. According to the researchers, IRF55 activates harmful macrophages, which cause inflammation.
In this latest study, the researchers wanted to prove that IRF5 was important in the development of obesity complications, such as type 2 diabetes. To do this, they engineered mice that did not have IRF5, and fed them a high-fat diet which would, in most cases, cause obesity and type 2 diabetes. The mice without IRF5 did become obese, which surprised the researchers, but they did not develop metabolic complications such as type 2 diabetes.
In fact, in the mice without IRF5, obesity triggered anti-inflammatory macrophages. This prevented the growth of intra-abdominal adipose tissue, which causes the inflammation problems in the first place. In other words, obese mice without IRF5 were protected from metabolic complications, because obesity triggers a different response when IRF5 is absent.
When the findings were applied to obese and overweight human subjects, the findings were consistent: when IRF5 was present, the individual was more likely to develop metabolic complications of obesity, such as type 2 diabetes.
“It is […] crucial to decipher the different aspects of inflammation in order to better understand the multifactorial diseases associated with obesity, such as type 2 diabetes,” the researchers wrote.
The study was conducted by teams led by Nicolas Venteclef, of Cordeliers Researcher Centre, and Irina Udalova, of the Kennedy Institute of Rheumatology and the University of Oxford.