Targeting sites of lymph-adipose interaction to transform the treatment of immuno-metabolic disease

Type 2 diabetes is underpinned by the development of insulin resistance. Insulin resistance is promoted by expansion, inflammation and metabolism changes in abdominal fat. Intestinal lymph flows through the abdominal fat. This thesis demonstrates that the intestinal lymphatic vasculature is highly dynamic, proliferative and leaky in obesity. Lymph leakage into fat causes fat expansion, inflammation and insulin resistance. Modulation of lymph composition through diet modification and inhibition of lymph leakage with medications successfully attenuates the lymphatic remodelling, fat changes and insulin resistance. This thesis suggests that lymph-fat interactions represent a novel treatment target for obesity and type 2 diabetes.