Is the mesentery the cause of obesity?
Scientists have identified the biological cause of obesity and diabetes
Australian scientists have for the first time established that the cause of obesity and insulin resistance is dysfunction of the lymphatic system of the mesentery – an organ of the human digestive system through which the hollow organs of the abdominal cavity are attached to the back wall of the abdomen. The results are published in the journal Nature Metabolism (Cao et al., Mesenteric lymphatic dysfunction promotes insulin resistance and represents a potential treatment target in obesity).
Scientists from the Melbourne Institute of Pharmaceutical Sciences at Monash University together with colleagues from the University of Melbourne, the University of Auckland and the University of South Australia in a preclinical study found that a high-fat diet stimulates the formation of a network of sinuous and branching lymphatic vessels in the mesentery.
These vessels, called mesenteric, tend to leak lymphatic fluid rich in intestinal lipid metabolites and inflammatory mediators into the visceral adipose tissue of the abdominal cavity, which causes the accumulation of abdominal fat and leads to insulin resistance.
"In this study, for the first time, we were able to uncover the biological reason why the accumulation of fat around the abdomen correlates with higher rates of metabolic diseases, such as type 2 diabetes, than the accumulation of fat in other parts of the body," the press release says. Monash University, the words of the head of the study, Associate Professor Natalie Trevaskis (Natalie Trevaskis). "We were able to show that a high–fat diet leads to dysfunction of mesenteric lymphatic vessels, which, in turn, contributes to the deposition of more fat in the abdominal area and insulin resistance."
The authors also presented experimental evidence that intervention in this cycle by inhibiting pathways associated with lymphatic dysfunction may become a new treatment for both obesity and related metabolic diseases. When COX-2 lymphatic cyclooxygenase inhibitor is administered to laboratory mice the structure of the mesenteric lymphatic vascular network was normalized in animals, weight gain was blocked and glucose intolerance and hyperinsulinemia – conditions associated with type 2 diabetes - were eliminated.
The success was achieved due to the fact that the researchers developed a method of targeted delivery of the inhibitor directly into the mesenteric lymphatic vessels using a specially developed drug. Scientists hope that this drug, after the necessary clinical trials, will become a new effective treatment for obesity and related metabolic diseases.
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