Lacteals, lymphatic vessels located at the center of each intestinal villus, play an important role in fat absorption. Their abnormalities in the structure and function may cause impaired lipid circulation, leading to obesity and abnormal lipid metabolism. We examined whether CGRP (calcitonin gene-related peptide) and its receptor, RAMP1 (receptor activity modifying protein 1), are involved in fat absorption via lacteals.
RAMP1 knockout (RAMP1 KO) and wild-type (WT) mice were fed a high-fat diet (HFD) or a normal diet (ND) for 8 weeks from 4 to 12 weeks of age. RAMP1KO mice given HFD increased body weight, adipose tissue mass, serum levels of total cholesterol, triglycerides, and blood glucose, and developed severe obesity compared to WT mice. In addition, the length of the lacteals tended to be shorter in HFD-fed RAMP1KO mice than in HFD-fed WT mice. On the other hand, no difference was observed when eating ND. HFD-fed RAMP1KO mice had decreased expression of lymphatic endothelial markers and pro-lymphangiogenic factors. After oral administration of BODIPY-FL-labelled C₁₆ fatty acids, the fluorescence intensity in blood in HFD-fed RAMP1KO mice was higher than that in HFD-fed WT mice.
These results suggest that CGRP/RAMP1 signaling is involved in the regulation of dietary fat absorption by the lacteals.