The Role of Macrophage Substrate Metabolism on Obesity-Induced Inflammation
Public Deposited- Last Modified
- February 26, 2019
- Creator
-
Huang, Megan
- Affiliation: Gillings School of Global Public Health, Department of Nutrition
- Abstract
- Obesity has become increasingly prevalent worldwide. Studies characterize obesity as a low-grade chronic state of inflammation and identify macrophages as having a role in this response. Macrophage polarization may influence the pro- and anti-inflammatory responses associated with obese and lean phenotypes, respectively. This study exploited the differences in substrate utilization between M1 and M2 polarized macrophages to observe whether there was a change in the inflammatory phenotype with obesity. M1-polarized macrophages are pro-inflammatory and use glucose as fuel whereas M2-polarized macrophages are anti-inflammatory and preferentially use fatty acids as fuel. Specifically in this experiment, mice containing macrophages that were FATP1 knockout or wildtype were fed either a low fat diet (10% kcal from fat, LFD)or a high fat diet (45% kcal from fat, HFD) to test our hypothesis that FATP1 is important in macrophage M2 polarization. Four groups were used in this experiment: low fat-fedwildtype and knockout (LFD FATP1B+/+ and LFD FATP1B-/-), and high fat-fedwildtype and knockout (HFD FATP1B+/+ and HFD FATP1B-/-). HFD FATP1B-/- mice gained more weight and had heavier epididymal white adipose tissue (eWAT) than HFD FATP1B+/+ mice. HFD FATP1B-/- also had higher percentage body fat and higher plasma leptin levels when compared to HFD FATP1B+/+ mice. HFD FATP1B-/- had higher expression of inflammatory markers in eWATcompared to HFD FATP1B+/+ mice. The HFD FATP1B-/- group had significantly increased expression of macrophage markers F4/80, CD11C, and CD11B in eWAT. Inflammatory cytokine IL6 was also significantly elevated in eWAT in HFD-fedFATP1B-/- mice when compared to HFD-fed FATP1B+/+ mice. Glucose transporter GLUT1 and components of the Nlrp3 inflammasomeexpressionwere also increased in HFD-fed FATP1B-/- in eWAT. Taken together, these data indicate that deletion of FATP1 from macrophages is associated with increased susceptibility to high fat diet-induced weight gain, increased macrophage adipose tissue infiltration, and a shift towards M1-like pro-inflammatory macrophage polarization. ThusM2 macrophages’ inability to use fatty acids as fuel drove a more pro-inflammatory phenotype. This study reveals insight into a possible mechanism for the polarization of macrophages that may be relevant to the propagation of obesity.
- Date of publication
- spring 2014
- Keyword
- DOI
- Resource type
- Rights statement
- In Copyright
- Note
- Funding: Tom and Elizabeth Long Excellence Fund for Honors
- Funding: Summer Undergraduate Research Fellowship
- Advisor
- Makowski, Liza
- Degree
- Bachelor of Science in Public Health
- Honors level
- Honors
- Degree granting institution
- University of North Carolina at Chapel Hill
- Extent
- 28
Relations
- Parents:
This work has no parents.