High Fat Diet Effects on Erythrophagocytosis and MCP-1 Levels in Mice

<p>Background: Atherosclerosis, characterized by the accumulation of lipid-laden plaques in vessel walls, is a known precursor to cardiovascular disease (CVD). Oxidation of cholesterol particles leads to endothelial damage and subsequent inflammation. Immune cells, such as monocytes, respond to chemokines and differentiate into macrophages, engulfing oxidized lipids, and forming foam cells within the vessel wall. Red blood cells (RBC) are known to bind chemokines through the Duffy antigen receptor for chemokines (DARC). RBCs may play a role in recruiting immune cells to lesions and contribute to the rupture of atherosclerotic plaques. Although exposure to a high fat diet (HFD) has been shown to alter RBC membrane properties, how this physiological change may affect RBC chemokine binding and macrophage interaction is less known.</p><p>Objective: To determine the effects of a high fat diet on murine RBC monocyte chemoattractant protein 1 (MCP-1) content and ex vivo murine macrophage erythrophagocytosis levels.</p><p>Methods: 6 week old C57BL/6 male mice were fed either chow diet (CD) as control (n=8) or a HFD (n=8) for 12 weeks. Body mass was measured upon arrival and at 18 weeks of age. Blood was collected via cardiac puncture and each sample divided into two treatments, one with heparin and one without for assessment of MCP-1 in total plasma and RBC bound. MCP-1 concentrations were measured by an ELISA for assessment of MCP-1 in total plasma and RBC bound. Erythrophagocytosis was determined ex vivo by exposing fluorescently labeled packed RBCs (pRBCs) to peritoneal macrophages harvested from C57BL/6 male mice fed a CD and measuring macrophage fluorescence. </p><p>Results: The HFD mice gained more weight over the 12 weeks than the CD mice (p < 0.01). Total plasma levels of MCP-1 increased in HFD mice compared to CD mice although the difference was not significant (p = 0.149). However, RBC bound MCP-1 levels increased significantly in HFD compared to CD (p < 0.05). Macrophage erythrophagocytosis was also 43% higher among the HFD mice as compared to the CD mice (p < 0.05). </p><p>Conclusion: The present study demonstrates that a high fat diet leads to increased likelihood of RBC clearance by macrophages, which could potentially contribute to inflammation. This change may be mediated by the altered RBC bound MCP-1 levels, although further work is necessary to determine cause and effect.</p>

Name thesis:degree_name

MS

Level thesis:degree_level

masters

Discipline thesis:degree_discipline

Allied Health Sciences: Nutrition

Grantor dc:publisher

University of Cincinnati

Year dc:date

2012

Author dc:creator

• Coyle, Danielle R.

Contributors dc:contributor

• Peairs, Abigail

• Nutrition
• Inflammation
• atherosclerosis
• RBC
• MCP-1
• high fat diet
• mice

Statement dc:rights

• unrestricted
• This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.

Language dc:language

English

Repository record dc:identifier

http://rave.ohiolink.edu/etdc/view?acc_num=ucin1353342118

OAI identifier oai:identifier

oai:etd.ohiolink.edu:ucin1353342118