title: Influence of dietary saturated fat content on adiposity, macrophage behavior, inflammation, and metabolism: composition matters.
abstract: 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)-α, interleukin (IL)-6, IL-10, suppressor of cytokine signaling (SOCS)1, IFN-γ] was measured along with activation of nuclear factor kappa-B (NFκB), 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.
authors.affiliation: Department of Pathology, Microbiology & Immunology, School of Medicine, University of South Carolina, Columbia, SC, USA.
authors.forename: Reilly T
authors.initials: RT
authors.lastname: Enos
authors.forename: J Mark
authors.initials: JM
authors.lastname: Davis
authors.forename: Kandy T
authors.initials: KT
authors.lastname: Velázquez
authors.forename: Jamie L
authors.initials: JL
authors.lastname: McClellan
authors.forename: Stani D
authors.initials: SD
authors.lastname: Day
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Carnevale
authors.forename: E Angela
authors.initials: EA
authors.lastname: Murphy
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D050154:Adiposity / Q000187:drug effects*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D059305:Diet, High-Fat / Q000009:adverse effects; D004041:Dietary Fats / Q000009:adverse effects*; D002149:Energy Intake / Q000187:drug effects; D005227:Fatty Acids / Q000009:adverse effects*; D007249:Inflammation / Q000097:blood / Q000209:etiology / Q000378:metabolism; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice
chemical_list: D004041:Dietary Fats; D005227:Fatty Acids; D020738:Leptin