Influence of dietary saturated fat content on adiposity, macrophage behavior, inflammation, and metabolism: composition matters

We examined the effects of three high-fat diets (HFD), differing in the percentage of total calories from saturated fat (SF) (6%, 12%, and 24%) but identical in total fat (40%), on body composition, macrophage behavior, inflammation, and metabolic dysfunction in mice. Diets were administered for 16 weeks. Body composition and metabolism [glucose, insulin, triglycerides, LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), total cholesterol (TC)] were examined monthly. Adipose tissue (AT) expression of marker genes for M1 and M2 macrophages and inflammatory mediators [Toll-like receptor (TLR)-2, TLR-4, MCP-1, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL- 10, suppressor of cytokine signaling (SOCS) 1, IFN-gamma] was measured along with activation of nuclear factor kappa-B (NF kappa B), c-Jun N-terminal kinase (JNK), and p38- mitogen-activated protein kinase (MAPK). AT macrophage infiltration was examined using immunohistochemistry. Circulating MCP-1, IL- 6, adiponectin, and leptin were also measured. SF content, independent of total fat, can profoundly affect adiposity, macrophage behavior, inflammation, and metabolic dysfunction. In general, the 12%-SF diet, most closely mimicking the standard American diet, led to the greatest adiposity, macrophage infiltration, and insulin resistance (IR), whereas the 6%-SF and 24%-SF diets produced lower levels of these variables, with the 24%-SF diet resulting in the least degree of IR and the highest TC/HDL-C ratio. Macrophage behavior, inflammation, and IR following HFD are heavily influenced by dietary SF content; however, these responses are not necessarily proportional to the SF percentage.-Enos, R. T., J. M. Davis, K. T. Velazquez, J. L. McClellan, S. D. Day, K. A. Carnevale, and E. A. Murphy. Influence of dietary saturated fat content on adiposity, macrophage behavior, inflammation, and metabolism: composition matters. J. Lipid Res. 2013. 54: 152-163.