The Lymphatic Vasculature: Its Role in Adipose Metabolism and Obesity

Abstract

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 the fact 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 lymphatic vessels 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 lymphatic-adipose tissue relationship.

Keywords: Prox1; adipose tissue; chyle; endothelial cell; inflammation; lymph; lymphatics; obesity.

Figure 1. Lymphatic vascular defects contribute to adult-onset obesity

In Prox1^+/− mice, compromised lymphatic vascular integrity causes subtle leakage of lymph. FFA-containing lymph accumulates in the nearby tissues, particularly in the visceral area where it induces de novo differentiation of fat cell precursors, fat cell hypertrophy and eventually adipocyte proliferation. With age, Prox1^+/− mice became progressively obese.

Figure 2. Presence of lymphatic vessels in fat depots of adult mice

Visceral fat depots were dissected and subject to whole mount immunostaining with antibodies against lymphatic endothelial cells (Lyve1, Prox1) and adipocytes (Perilipin). Lymphatic vessels are seen deep inside the WAT and nearby blood vessels (not shown). LV: lymphatic vessel. Scale bar 30 uM.