Influence of High Fat Diet on Macrophage Behavior and Metabolic Processes in Obesity Sensitive and Resistant Mice: Role of Monocyte Chemoattractant Protein 1

Abstract

PURPOSEAdipose tissue macrophages are thought to be a major player in the dysregulation of metabolic and inflammatory processes associated with high fat diet (HFD)‐induced obesity. Monocyte chemoattractant protein 1 (MCP‐1) is a chemokine that recruits macrophages to adipose tissue (AT) and has been implicated in manifestations associated with obesity. The purpose of this study was to examine the role of MCP‐1 in response to HFD feedings. We used both C57Bl/6 (obesity sensitive) and FVB/N (obesity resistant) mice in order to determine obesity versus HFD effects. A HFD that was designed by our laboratory and is similar to a standard American diet was used given its clinical relevance.METHODSC57Bl/6 and FVB/N wild‐type (WT) and MCP1‐/‐ mice at 4 wks of age were fed either a HFD or a low fat diet (LFD) for 16 wks. Body composition was analyzed monthly and HOMA index was determined at mice sacrifice at 20 wks of age. AT mRNA expression of chemokines, macrophage markers and protein expression of inflammatory markers were measured using qPCR and western blot, respectively. Macrophage infiltration into AT were examined using immunohistochemistry and flow cytometry.RESULTSAs expected, HFD induced obesity and increased insulin resistance (IR) comparably in the obesity sensitive C57Bl/6 WT and MCP1‐/‐ mice. Surprisingly, the HFD MCP1‐/‐ in the supposed diet resistant FVB/N strain exhibited increased obesity and IR whereas the HFD WT mice were not different from LFD mice. AT macrophage accumulation increased in HFD WT groups for both strains, regardless of obesity status. Interestingly, the response in HFD MCP1‐/‐ was dependent on the strain.