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- Title
Deletion of RAMP1 Signaling Enhances Diet-induced Obesity and Fat Absorption via Intestinal Lacteals in Mice.
- Authors
KANAKO HOSONO; ATSUSHI YAMASHITA; MINA TANABE; YOSHIYA ITO; MASATAKA MAJIMA; KAZUTAKE TSUJIKAWA; HIDEKI AMANO
- Abstract
Background/Aim: Intestinal lymphatic vessels (lacteals) play a critical role in the absorption and transport of dietary lipids into the circulation. Calcitonin gene-related peptide and receptor activity-modifying protein 1 (RAMP1) are involved in lymphatic vessel growth. This study aimed to examine the role of RAMP1 signaling in lacteal morphology and function in response to a high-fat diet (HFD). Materials and Methods: RAMP1 deficient (RAMP1-/-) or wild-type (WT) mice were fed a normal diet (ND) or HFD for 8 weeks. Results: RAMP1-/- mice fed a HFD had increased body weights compared to WT mice fed a HFD, which was associated with high levels of total cholesterol, triglycerides, and glucose. HFD-fed RAMP1-/- mice had shorter and wider lacteals than HFD-fed WT mice. HFD-fed RAMP1-/- mice had lower levels of lymphatic endothelial cell gene markers including vascular endothelial growth factor receptor 3 (VEGFR3) and lymphatic vascular growth factor VEGF-C than HFD-fed WT mice. The concentration of an absorbed lipid tracer in HFD-fed RAMP1-/- mice was higher than that in HFD-fed WT mice. The zipper-like continuous junctions were predominant in HFD-fed WT mice, while the button-like discontinuous junctions were predominant in HFD-fed RAMP1-/- mice. Conclusion: Deletion of RAMP1 signaling suppressed lacteal growth and VEGF-C/VEGFR3 expression but accelerated the uptake and transport of dietary fats through discontinuous junctions of lacteals, leading to excessive obesity. Specific activation of RAMP1 signaling may represent a target for the therapeutic management of diet-induced obesity.
- Subjects
OBESITY; CALCITONIN gene-related peptide; CELLULAR signal transduction; VASCULAR endothelial growth factor receptors; LABORATORY mice
- Publication
In Vivo, 2024, Vol 38, Issue 1, p160
- ISSN
0258-851X
- Publication type
Article
- DOI
10.21873/invivo.13422