"Gut Lymphatics in Metabolism, Inflammation and Immune Cell Regulation"

Mariappan Muthuchamy, Ph.D.
Professor
Department of Medical Physiology
Texas A&M Health Science Center

Metabolic syndrome (MetSyn) is defined by the cluster of 3 or more of the following physiologic or metabolic abnormalities: central obesity, elevated fasting glucose levels, dyslipidemia, hypertension, and intimal atherogenesis. These lead to increased risks for the development of type 2 diabetes, fatty liver disease and atherosclerotic vascular disease. Since the progression of MetSyn leads to cardiovascular diseases and because of it’s heterogeneous characteristics, most current research has focused on studying the mechanisms of hypertension, atherosclerosis, inflammation, nutrition, metabolism and insulin resistance. However the gut lymphatic network is where >95% of the dietary lipids are absorbed from the intestine and transported to blood thus regulating lipid metabolism; hence we asked the question whether the lymphatic function is compromised in MetSyn. Our data demonstrate that high fructose diet-induced MetSyn rats exhibit significant decreases in phasic contractile frequency, thereby reducing the intrinsic lymph pump flow. Lymphatic muscle force generation was also significantly reduced and was accompanied by decreased calcium (Ca2+) sensitivity in the MetSyn lymphatic muscle. In addition, the expression of TNF- in the liver was increased in the MetSyn animals. Furthermore an increase in macrophage (MØ) recruitment to the wall and near the vicinity of mesenteric lymphatics with a shift to a predominantly inflammatory M1-polarization demonstrates the inflammatory state of the mesentery in MetSyn rats. In our laboratory we use the high-fructose diet-induced MetSyn rat model and a LPS-induced inflammation model to determine the molecular mechanisms involving inflammation, immune cell regulation and lymphatic function in the pathophysiology of MetSyn.