Micro- and Macro-Anatomical Frameworks of Lymph Nodes Indispensable for the Lymphatic System Filtering Function.

In the lymphatic vascular system, lymph nodes (LNs) play a pivotal role in filtering and removing lymph-borne substances. The filtering function of LNs involves resident macrophages tightly associated with unique lymphatic sinus structures. Moreover, an intermittently arranged LN in the lymphatic pathway is considered to cooperatively prevent lymph-borne substances from entering blood circulation. However, the functional significance of tissue microarchitecture, cellular composition, and individual LNs in the "LN chain" system is not fully understood. To explore the mechanistic and histo-anatomical significance of LNs as lymph fluid filters, we subcutaneously injected fluorescent tracers into mice and examined the details of lymphatic transport to the LNs qualitatively and quantitatively. Lymph-borne tracers were selectively accumulated in the MARCO+ subcapsular-medullary sinus border (SMB) region of the LN, in which reticular lymphatic endothelial cells and CD169+F4/80+ medullary sinus macrophages construct a dense meshwork of the physical barrier, forming the main body to capture the tracers. We also demonstrated stepwise filtration via the LN chain in the lymphatic basin, which prevented tracer leakage into the blood. Furthermore, inflammatory responses that induce the remodeling of LN tissue as well as the lymphatic pathway reinforce the overall filtering capacity of the lymphatic basin. Taken together, specialized tissue infrastructure in the LNs and their systematic orchestration constitute an integrated filtering system for lymphatic recirculation.

Analysis of anti-obesity and anti-diabetic effects of acacia bark-derived proanthocyanidins in type 2 diabetes model KKAy mice.

The acacia bark extract derived from Acacia mearnsii De Wild is rich in proanthocyanidins, whose constituent units are robinetinidol, fisetinidol, catechin, and gallocatechin. In this study, we examined the effect of proanthocyanidins on obesity and diabetes using KKAy mice, a type 2 diabetes model. KKAy mice were fed either a low-fat diet, a high-fat diet, or a high-fat diet mixed with an acacia bark extract, a proanthocyanidins fraction, and other fraction for 7 weeks. Monitoring the changes in the body weight revealed that acacia bark extract and proanthocyanidins fraction could prevent excessive weight gain resulting from a high-fat diet. In addition, increases in the fasting blood glucose level due to high-fat diet intake were found to be suppressed by acacia bark extract and proanthocyanidins fraction. Furthermore, proanthocyanidins derived from acacia bark were found to increase the expression of adiponectin in white adipose tissue, which enhances the action of insulin. In addition, acacia bark-derived proanthocyanidins suppressed gluconeogenesis and fatty acid synthesis in the liver, as well as suppressing the decrease in energy production under pathological conditions in skeletal muscle. In addition, acacia bark-derived proanthocyanidins showed AMPK activation and DPP-4 inhibitory action. Therefore, it was suggested that acacia bark-derived proanthocyanidins lowered fasting blood glucose levels through the above mechanism. These results suggest that proanthocyanidins derived from acacia bark are the active ingredients of the anti-obesity and anti-diabetic effects of acacia bark extract.