Abstract
Obesity has been associated with increased susceptibility to infection in humans and rodents. Obesity is also associated with low-grade hypothalamic inflammation that depends not only on body weight but also on diet. In the present study, we investigated if the bacterial endotoxin [lipopolysaccharide (LPS)]-induced acute phase response is aggravated in rats on a 1-week free-choice high-fat high-sugar (fcHFHS) diet and explained by diet-induced hypothalamic inflammation. Male Wistar rats were on an fcHFHS diet or chow for 1 week and afterwards intraperitoneally injected with LPS or saline. Hypothalamic inflammatory intermediates and plasma cytokines were measured after LPS. Both LPS and the fcHFHS diet altered hypothalamic Nfkbia mRNA and nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor alpha (NFKBIA) protein levels, whereas Il1β, Il6, and Tnfα mRNA expression was solely induced upon LPS. We observed an interaction in hypothalamic Nfkbia and suppressor of cytokine signaling (SOCS) 3 mRNA upon LPS; both were higher in rats on a fcHFHS diet compared with chow animals. Despite this, plasma cytokine levels between fcHFHS diet-fed and chow-fed rats were similar after LPS administration. Consuming a fcHFHS diet but not LPS injections increased hypothalamic Atf4 (a cellular stress marker) mRNA expression, whereas Tlr4 mRNA was decreased only upon LPS. Our study does not support a role for diet-induced mild hypothalamic inflammation in the increased susceptibility to infection despite altered Nfkbia and Socs3 mRNA expression after the diet. Additional factors, related to increased fat mass, might be involved.
Highlights
Obesity is shown to be associated with increased susceptibility to post-operative infections in humans [1,2,3,4] and experimental induced infection in rodents [5,6,7]
LPS administration and free-choice high-fat high-sugar (fcHFHS) diet independently resulted in decreased NFKBIA protein levels (Figures 1A,B), whereas the Nfkbia mRNA response to LPS was more severe in animals on the fcHFHS diet compared with chow-fed animals
The aim of the present study was to determine whether the higher susceptibility to infection, shown to occur in obesity is mediated by diet-induced hypothalamic low-grade inflammation
Summary
Obesity is shown to be associated with increased susceptibility to post-operative infections in humans [1,2,3,4] and experimental induced infection in rodents [5,6,7]. NF-κB is one of the mediators involved in the acute phase response upon infection via degradation of the nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor alpha (NFKBIA), allowing activation of NF-κB by phosphorylation (p-NF-κB). These events lead to increased mRNA and protein expression of cytokines and the negative feedback regulators of inflammatory signaling SOCS3 [12, 13]
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