Mice Chronically Fed High-Fat Diet Have Increased Mortality and Disturbed Immune Response in Sepsis

Abstract

BackgroundSepsis is a potentially deadly disease that often is caused by gram-positive bacteria, in particular Staphylococcus aureus (S. aureus). As there are few effective therapies for sepsis, increased basic knowledge about factors predisposing is needed.Methodology/Principal FindingsThe purpose of this study was to study the effect of Western diet on mortality induced by intravenous S. aureus inoculation and the immune functions before and after bacterial inoculation. Here we show that C57Bl/6 mice on high-fat diet (HFD) for 8 weeks, like genetically obese Ob/Ob mice on low-fat diet (LFD), have increased mortality during S. aureus-induced sepsis compared with LFD-fed C57Bl/6 controls. Bacterial load in the kidneys 5–7 days after inoculation was increased 10-fold in HFD-fed compared with LFD-fed mice. At that time, HFD-fed mice had increased serum levels and fat mRNA expression of the immune suppressing cytokines interleukin-1 receptor antagonist (IL-1Ra) and IL-10 compared with LFD-fed mice. In addition, HFD-fed mice had increased serum levels of the pro-inflammatory IL-1β. Also, HFD-fed mice with and without infection had increased levels of macrophages in fat. The proportion and function of phagocytosing granulocytes, and the production of reactive oxygen species (ROS) by peritoneal lavage cells were decreased in HFD-fed compared with LFD-fed mice.ConclusionsOur findings imply that chronic HFD disturb several innate immune functions in mice, and impairs the ability to clear S. aureus and survive sepsis.

Dietary Omega-3 Fatty Acids Increase Survival and Decrease Bacterial Load in Mice Subjected to Staphylococcus aureus-Induced Sepsis

“…Further, the saturated fatty acid content in serum of mice fed HFD-S was not increased after 8 weeks. Our findings agree with our previous studies showing that mice fed HFD-S have an impaired immune response compared to that of mice fed LFD (9). The findings of this study are also in line with our recent finding that mice fed HFD-P have greater survival and a higher determine statistically significant differences (n ϭ 10 mice per group).…”

“…In previous studies by our research group, we found that the immune system was negatively affected by high-fat diet (HFD) rich in saturated fatty acids (HFD-S), resulting in decreased survival of septic S. aureus-induced infection, compared with a lowfat diet (LFD) (9). Interestingly, in a later study, we found that mice fed HFD rich in polyunsaturated fatty acids (HFD-P) had increased survival of septic S. aureus-induced infection and decreased bacterial loads in the kidneys compared with those for mice fed HFD-S (10).…”

Dietary Polyunsaturated Fatty Acids Increase Survival and Decrease Bacterial Load during Septic Staphylococcus aureus Infection and Improve Neutrophil Function in Mice

“…These findings confirm and extend our previous study showing impaired immune response in mice fed HFD-S compared with mice fed LFD (16). The present study implicates that high-fat diet per se is not necessarily deleterious, but rather that a high grade of saturation of the fat impairs the immune response.…”

“…Mice were infected i.v. in the tail vein with 0.2 ml S. aureus LS-1 solution containing 3.8 ϫ 10 7 to 4.5 ϫ 10 7 CFU, as previously described (16). For bacterial load determination, the mice were killed 6 days after i.v.…”

“…We have previously observed that mice fed a saturated high-fat diet (HFD-S) have decreased survival when subjected to septic S. aureus infection compared with mice fed a low-fat diet (LFD) (16). Moreover, mice fed HFD-S displayed increased bacterial load, suggesting that their immune system has an impaired capacity to prevent bacterial survival and replication compared with that of mice fed LFD (16). In the present study, we aimed to compare how polyunsaturated and saturated dietary fats affect survival and immune response in sepsis.…”