The Role of Lymphatic System in the Regulation and Maintenance of Energy Homeostasis

Dear Colleagues,

The lymphatic system (LS) ensures fluid balance within the body, the trafficking and proper activation of immune cells, and the transport of lipids and interstitial macromolecules that cannot cross the endothelial barrier.  As such, it is essential for the interorgan communication, the immune status of tissues, and proper lipid distribution. These qualities predispose the LS to be a regulator of many physiological processes including those occurring in the trinity of organs implicated in energy homeostasis: the liver, skeletal muscle and adipose tissue. However, the current understanding of the physiologic role of the LS in these organs remains close to zero, as the homeostatic role of the LS is frequently disregarded until comorbidities associated with its severe dysfunction develop.

The liver, an organ crucial for the synthesis of lipids and glucose, as well as for the regulation of insulin sensitivity, produces up to 50% of the lymph passing through the thoracic duct. The majority of the proteins synthesized by the liver are secreted and presumably reach the blood via lymph. In cirrhosis, lymph production by the liver increases up to 30 fold, and the incapability of the LS to deal with such an overload leads to the formation of ascites. Skeletal muscle and adipose tissue are also rich sources of cytokines reaching the blood via lymphatics, and thus, LS function could regulate signaling among these tissues as well as being important for the proper regeneration of muscle after intense workouts and the systemic availability of released lipid substrates. Indications that the LS may profoundly affect the physiology of adipose tissue come mostly from research into severe lymphatic dysfunctions manifested by the development of lymphedema. Lymphedema has been associated with the abnormal accumulation of adipose tissue preceded by adipose tissue inflammation and fibrosis, although the exact trigger of these changes is still unclear. Moreover, it could also be envisioned that the lymphatic system regulates the infiltration of these insulin-sensitive tissues with immune cells, and thus, subtle individual alterations in the LS’ efficacy could impact their immunophenotype and functionality and contribute to the development of metabolic diseases. 

On the other side, the acquired dysfunction of these organs or nutrient dysbalances can further worsen the function of the LS, including changes to lymphatic permeability, contractility and transport properties and the alteration of lymph node structure. Despite these facts, the knowledge of the LS’ function in physiological and various pathophysiological states related to metabolism is surprisingly limited.

To this end, we would like to welcome submissions in the form of reviews and/or original research presenting new advances in the potential involvement of the LS in the regulation of the properties and functions of the liver, skeletal muscle and adipose tissue in the context of metabolism, gender, lifestyle interventions, obesity, diabetes and related comorbidities, including novel data from relevant animal models, human cohorts and interventional clinical studies.

Dr. Lenka Rossmeislová
Guest Editor

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• lymphatic system
• lymphatic drainage
• liver
• skeletal muscle
• adipose tissue
• metabolism
• insulin resistance
• diabetes
• lifestyle intervention
• gender differences