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The effect of a high-fat diet on murine macrophage activity
J L Stewart-Phillips1, J Lough, N C Phillips
1Montreal General Hospital Research Institute, Quebec, Canada.
Abstract:
The phagocytic, oxygen free radical generating and cytotoxic activities of macrophages from C57BL/6J mice fed either a normal or an atherogenic high-fat diet have been investigated. Phagocytosis of aggregated low density lipoprotein (LDL) was only slightly inhibited by the high-fat diet although phorbol myristate acetate (PMA)-induced hydrogen peroxide (H2O2) and superoxide anion (O2-) production was significantly reduced. Activation of tumoricidal activity against L929 target cells by lipopolysaccharide (LPS) or lymphocyte-derived macrophage-activating factor (MAF), but not N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP), was also significantly reduced in macrophages from mice fed the high-fat diet. These results indicate that an atherogenic diet is capable of significantly affecting the responsiveness of macrophages to a number of stimulatory agents which act via specific membrane receptors.
Insights
An atherogenic diet impairs macrophage function, reducing their ability to produce reactive oxygen species and activate anti-tumor activity. This highlights how diet impacts immune cell responsiveness.
Area of Science:
- Immunology
- Nutrition Science
- Cell Biology
Background:
- Macrophages play a crucial role in immune responses and are implicated in atherosclerosis.
- Dietary factors, particularly high-fat diets, can influence immune cell function.
- Understanding how atherogenic diets affect macrophage activity is vital for metabolic and immune health.
Purpose of the Study:
- To investigate the impact of an atherogenic high-fat diet on the functional activities of macrophages.
- To assess changes in phagocytic, reactive oxygen species (ROS) production, and cytotoxic functions of macrophages.
Main Methods:
- C57BL/6J mice were fed either a normal or an atherogenic high-fat diet.
- Macrophage phagocytosis of aggregated low-density lipoprotein (LDL) was measured.
- Phorbol myristate acetate (PMA)-induced hydrogen peroxide (H2O2) and superoxide anion (O2-) production were quantified.
- Tumoricidal activity against L929 target cells was assessed following stimulation with lipopolysaccharide (LPS), macrophage-activating factor (MAF), or N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP).
Main Results:
- Phagocytosis of aggregated LDL was only slightly inhibited by the high-fat diet.
- PMA-induced hydrogen peroxide (H2O2) and superoxide anion (O2-) production were significantly reduced in macrophages from mice on the high-fat diet.
- Activation of tumoricidal activity by LPS or MAF was significantly reduced, while MDP-induced activation was not significantly affected.
Conclusions:
- An atherogenic diet significantly impairs macrophage responsiveness to various stimulatory agents.
- The diet affects key macrophage functions, including reactive oxygen species generation and cytotoxic potential.
- These findings suggest a direct link between dietary fat intake and compromised immune cell function, potentially contributing to disease pathogenesis.