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.
Highlights
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
The extent to which the fatty acids (FA) composition of a HFD influences macrophage behavior and inflammation is still poorly understood; most of the available supporting literature is limited by the lack of control for various nutrients, the utilization of a single ingredient as the sole source of dietary fat, and the absence of dose response studies
We examined the effect of three HFDs, differing in the percentage of total calories from SF (6%, 12%, and 24%) but identical in total fat (40%), on adiposity, macrophage phenotype, inflammation, and metabolism utilizing controlled diets consisting of various lipid-rich ingredients
Summary
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. Influence of dietary saturated fat content on adiposity, macrophage behavior, inflammation, and metabolism: composition matters. There has been a major emphasis on understanding the link between high-fat-diet-induced obesity and chronic disease risk In this context, low-grade chronic inflammation has emerged as a key pathogenic link [3,4,5]. It is widely accepted that high-fat-diet-induced obesity can lead to a chronic state of low-grade inflammation. This is largely mediated through quantitative and functional alterations in white adipose tissue macrophages (ATM) [6, 7].
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