Regulation of Lymphatic Function in Obesity

Abstract

The lymphatic system has many functions, including macromolecules transport, fat absorption, regulation and modulation of adaptive immune responses, clearance of inflammatory cytokines, and cholesterol metabolism. Thus, it is evident that lymphatic function can play a key role in the regulation of a wide array of biologic phenomenon, and that physiologic changes that alter lymphatic function may have profound pathologic effects. Recent studies have shown that obesity can markedly impair lymphatic function. Obesity-induced pathologic changes in the lymphatic system result, at least in part, from the accumulation of inflammatory cells around lymphatic vessel leading to impaired lymphatic collecting vessel pumping capacity, leaky initial and collecting lymphatics, alterations in lymphatic endothelial cell (LEC) gene expression, and degradation of junctional proteins. These changes are important since impaired lymphatic function in obesity may contribute to the pathology of obesity in other organ systems in a feed-forward manner by increasing low-grade tissue inflammation and the accumulation of inflammatory cytokines. More importantly, recent studies have suggested that interventions that inhibit inflammatory responses, either pharmacologically or by lifestyle modifications such as aerobic exercise and weight loss, improve lymphatic function and metabolic parameters in obese mice. The purpose of this review is to summarize the pathologic effects of obesity on the lymphatic system, the cellular mechanisms that regulate these responses, the effects of impaired lymphatic function on metabolic syndrome in obesity, and the interventions that may improve lymphatic function in obesity.

Keywords: inflammation; lymphatic function; lymphatic vessels; metabolic syndrome; obesity.

FIGURE 1

Reciprocal regulation of obesity and lymphatic dysfunction. Schematic illustration showing the reciprocal regulation of obesity and lymphatic dysfunction. Peri-lymphatic inflammation in obesity causes decreased lymphatic pumping, DC migration, LEC gene expression, and increased lymphatic leakage leading to lymphatic dysfunction. Behavioral interventions like aerobic exercise and weight loss inhibit and reverse obesity-induced lymphatic dysfunction. Genetic or surgical lymphatic damage or dysfunction causes malabsorption of lipids, adipocyte proliferation, and progressive accumulation of adipose tissue, leading to obesity.