The lymphatic vasculature: its role in adipose metabolism and obesity
A review article on the mechanisms by which defective lymphatics contribute to obesity and fat accumulation in mouse models, as well as the relationship of the lymphatics-adipose tissue.
Obesity is a key risk factor for metabolic and cardiovascular diseases, and although we understand the mechanisms regulating weight and energy balance, the causes of some forms of obesity remain enigmatic. Despite the well-established connections between lymphatics and lipids, and that intestinal lacteals play key roles in dietary fat absorption, the function of the lymphatic vasculature in adipose metabolism has only recently been recognized. It is well established that angiogenesis is tightly associated with the outgrowth of adipose tissue, as expanding adipose tissue requires increased nutrient supply from blood vessels. Results supporting a crosstalk between lymphatics and adipose tissue, and linking lymphatic function with metabolic diseases, obesity and adipose tissue also started to accumulate in the last years. Here we review our current knowledge of the mechanisms by which defective lymphatics contribute to obesity and fat accumulation in mouse models, as well as our understanding of the lymphatics-adipose tissue relationship.
Finally, it is critical to emphasize that blood vessels, adipocytes, lymphatic vessels, macrophages and immune cells all coexist and interact extensively within the adipose tissue, therefore the future treatment of obesity and associated disorders should be focused on multiple therapies considering all these factors and its possible consequences. Additionally, those findings of lymphedema-induced obesity call for translation into clinical applications, and suggest that ‘lymphatic endothelial therapy’ can also be applied for obesity treatment. For example, specific inhibitors of the VEGF-C/VEGFR-3 signaling pathway could provide benefits for the treatment of obesity by reducing the absorption of excess dietary lipids and regulating insulin resistance.