Researchers discover a possible cause and therapies for insulin resistance and obesity

Oct, 2021 - By SMI

Monash University researchers have demonstrated that mesenteric lymphatic dysfunction is a possible cause and therapeutic target for insulin resistance and obesity.

The pioneering research discovered a harmful cycle where a diet with high fat causes mesenteric lymphatic malfunction, which results in abdominal fat accumulation. Furthermore, the research suggests that interfering with this series by suppressing pathways linked to lymphatic dysfunction could be a therapy for obesity and related metabolic ailment. Treatments of the mesenteric lymphatic system by a lymph-targeted COX-2 inhibitor were demonstrated to regulate the lymphatic vascular structure, prevent excess weight, and restore glucose intolerance, as well as the hyperinsulinemia - symptoms of type-2 diabetes.

A diet with a high amount of fat accelerated the development of novel mesenteric lymphatic vessels in a very disordered pattern, as observed in pre-clinical models. These twisted, branching vessels appeared to outflow lymphatic fluid into the visceral adipose tissue in the belly, which caused insulin resistance by being rich in gut-derived lipid compounds and pro-inflammatory mediators.

The adoption of Glyph prodrug technology platform by PureTech, which is especially aimed at enabling the operating of small molecule drugs straight into the mesenteric lymphatic system by oral administration, was vital to the study's success. Since it delivered the COX-2 inhibitor precisely to where it was needed in the mesenteric lymphatics, lymph targeting technology was critical in the current study for interrupting the cycle wherein the mesenteric lymphatic dysfunction leads to the formation of abdominal fat.

PureTech's Chief Scientific Officer, Joseph Bol stated that what is impressive about such a study is that when the COX-2 inhibitor was delivered directly to the mesenteric lymphatics with the Glyph technology platform, it was able to implicitly repattern the chaotic lymphatic structure in overweight mice and that repatterning was accompanied by a significant reduction in both gaining weight and insulin resistance. They are excited to continue their long-term collaboration with the Monash team to expand on this interesting study and uncover and advance new possible medical uses for this platform.