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

Journal article
Authors Louise Strandberg
Margareta Verdrengh
Maria Enge
Niklas Andersson
Sylvie Amu
Karin Önnheim
Anna Benrick
Mikael Brisslert
Johan Bylund
Maria Bokarewa
Staffan Nilsson
John-Olov Jansson
Published in PloS one
Volume 4
Issue 10
Pages e7605
ISSN 1932-6203
Publication year 2009
Published at Institute of Neuroscience and Physiology, Department of Physiology
Department of Mathematical Sciences, Mathematical Statistics
Institute of Medicine, Department of Rheumatology and Inflammation Research
Pages e7605
Language en
Links dx.doi.org/10.1371/journal.pone.000...
Subject categories Physiology

Abstract

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. METHODOLOGY/PRINCIPAL FINDINGS: 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.

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