Brain Inflammatory Mediators induced by high fat diet are significantly blunted with the deletion of MCP‐1

Abstract

Consumption of a high fat diet (HFD) can lead to central nervous system (CNS) inflammation. Monocyte chemoattractant protein (MCP‐1) is fundamental in the release of inflammatory mediators, but its role in HFD induced CNS inflammation has not yet been determined. The purpose of this study was to determine the role of MCP‐1 on brain inflammation following 15 weeks of HFD feedings. C57BL/6 wildtype mice (n=20) and MCP‐1 −/− mice (n=32), 4 weeks of age were randomly assigned to one of four groups: normal diet wildtype (ND‐WT), HFD wildtype (HFD‐WT), normal diet MCP‐1−/− (ND‐MCP‐1−/−) or HFD MCP‐1 −/− (HFD‐MCP‐1−/−). The mice were fed the HFD (41% of total caloric intake from fat) or normal diet (11.5% of total caloric intake from fat) for 15 weeks. Mice were sacrificed at 19 weeks of age and the brainstem was dissected and analyzed for mRNA gene expression of TLR4, F4/80, CD11c and TNF‐α using real time RT‐PCR. Gene expression of TLR4, CD11c and TNF‐α was increased in the brainstem of HFD‐WT relative to ND‐WT (p<0.05), whereas HFD‐MCP‐1−/− was not different from ND‐WT. A similar effect was observed for F4/80, but this did not reach statistical significance. No differences were found among the other groups. These data support a necessary role of MCP‐1 on the brain inflammatory response following HFD feedings. MCP‐1 may be an important therapeutic target in HFD‐induced brain inflammation.