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Front. Endocrinol. | doi: 10.3389/fendo.2018.00186

One-week exposure to a free-choice high-fat high-sugar diet does not interfere with the lipopolysaccharide-induced acute phase response in the hypothalamus of male rats.

  • 1Endocrinology and Metabolism, Academic Medical Center (AMC), Netherlands

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 (LPS)-induced acute phase response is aggravated in rats on a one-week free-choice high-fat high-sugar (fcHFHS) diet and explained by diet-induced hypothalamic inflammation. Male Wistar rats were on a fcHFHS diet or chow for one 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 NFKBIA protein levels, whereas Il1β, Il6 and Tnfα mRNA expression was solely induced upon LPS. We observed an interaction in hypothalamic Nfkbia and Socs3 mRNA upon LPS; both were higher in rats on a fcHFHS diet compared to 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 NF-κB and SOC3 mRNA expression after the diet. Additional factors, related to increased fat mass, might be involved.

Keywords: Hypothalamus, Diet, Obesity, lipopolysaccharide, Cytokines, er stress

Received: 06 Dec 2017; Accepted: 06 Apr 2018.

Edited by:

Margaret Morris, University of New South Wales, Australia

Reviewed by:

Christelle Le Foll, Universität Zürich, Switzerland
Kathleen G. Mountjoy, University of Auckland, New Zealand
Michael Kendig, University of New South Wales, Australia  

Copyright: © 2018 Belegri, Eggels, la Fleur and Boelen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Anita Boelen, Academic Medical Center (AMC), Endocrinology and Metabolism, Meibergdreef 9,, Amsterdam, 1105AZ, Netherlands, a.boelen@amc.uva.nl