Mice chronically fed high-fat diet have increased mortality and disturbed immune response in sepsis.
BACKGROUND
Sepsis 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.


RESULTS
The 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-1beta. 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.


CONCLUSIONS
Our findings imply that chronic HFD disturb several innate immune functions in mice, and impairs the ability to clear S. aureus and survive sepsis.
Institute of Neuroscience and Physiology/Endocrinology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Louise
L
Strandberg
Margareta
M
Verdrengh
Maria
M
Enge
Niklas
N
Andersson
Sylvie
S
Amu
Karin
K
Onnheim
Anna
A
Benrick
Mikael
M
Brisslert
Johan
J
Bylund
Maria
M
Bokarewa
Staffan
S
Nilsson
John-Olov
JO
Jansson
D000821:Animal Feed; D000818:Animals; D018752:Diet, Fat-Restricted; D004041:Dietary Fats / Q000494:pharmacology*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008957:Models, Genetic; D009765:Obesity / Q000150:complications / Q000235:genetics* / Q000276:immunology*; D018805:Sepsis / Q000150:complications* / Q000276:immunology* / Q000401:mortality*; D013203:Staphylococcal Infections / Q000150:complications / Q000401:mortality; D013211:Staphylococcus aureus / Q000378:metabolism; D013997:Time Factors
D004041:Dietary Fats; D053590:Interleukin 1 Receptor Antagonist Protein; D016753:Interleukin-10