Intravital imaging of intestinal lacteals unveils lipid drainage through contractility

• Published in: The Journal of clinical investigation Vol. 125; no. 11; pp. 4042 - 4052
• Main Authors: Choe, Kibaek, Jang, Jeon Yeob, Park, Intae, Kim, Yeseul, Ahn, Soyeon, Park, Dae-Young, Hong, Young-Kwon, Alitalo, Kari, Koh, Gou Young, Kim, Pilhan
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01.11.2015
• Subjects: Animals; Autonomic Nervous System - physiology; Biological Transport; Biomedical research; Cloning; Coloring Agents - pharmacokinetics; Diagnostic imaging; Dietary Fats - pharmacokinetics; Drugs; Enterocytes - metabolism; Fatty Acids - pharmacokinetics; Fluorescent Dyes - pharmacokinetics; Genes, Reporter; Genetic aspects; Green fluorescent protein; Green Fluorescent Proteins - analysis; Homeodomain Proteins - genetics; Intestinal Absorption - physiology; Intestinal Mucosa - ultrastructure; Intestine, Small - metabolism; Intravital Microscopy; Lipids; Lymphatic Vessels - drug effects; Lymphatic Vessels - innervation; Lymphatic Vessels - physiology; Lymphatic Vessels - ultrastructure; Metabolism; Methods; Mice; Mice, Inbred C57BL; Microscopy; Microscopy, Video; Microvilli - physiology; Muscle contraction; Muscle Contraction - drug effects; Muscle, Smooth - physiology; Norepinephrine - pharmacology; Permeability; Properties; Rodents; Small intestine; Studies; Tumor Suppressor Proteins - genetics
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI76509

Lacteals are lymphatic vessels located at the center of each intestinal villus and provide essential transport routes for lipids and other lipophilic molecules. However, it is unclear how absorbed molecules are transported through the lacteal. Here, we used reporter mice that express GFP under the control of the lymphatic-specific promoter Prox1 and a custom-built confocal microscope and performed intravital real-time visualization of the absorption and transport dynamics of fluorescence-tagged fatty acids (FAs) and various exogenous molecules in the intestinal villi in vivo. These analyses clearly revealed transepithelial absorption of these molecules via enterocytes, diffusive distribution over the lamina propria, and subsequent transport through lacteals. Moreover, we observed active contraction of lacteals, which seemed to be directly involved in dietary lipid drainage. Our analysis revealed that the smooth muscles that surround each lacteal are responsible for contractile dynamics and that lacteal contraction is ultimately controlled by the autonomic nervous system. These results indicate that the lacteal is a unique organ-specific lymphatic system and does not merely serve as a passive conduit but as an active pump that transports lipids. Collectively, using this efficient imaging method, we uncovered drainage of absorbed molecules in small intestinal villus lacteals and the involvement of lacteal contractibility.