A chronic LPS-induced low-grade inflammation fails to reproduce in lean mice the impairment of preference for oily solution found in diet-induced obese mice

Arnaud Bernard,Déborah Ancel,Patricia Passilly-Degrace,Jean-François Landrier,Laurent Lagrost,Philippe Besnard

doi:10.1016/j.biochi.2018.08.004

Abstract

Diet-induced obesity (DIO) is associated with a decreased oral fat detection in rodents. This alteration has been explained by an impairment of the lipid-mediated signaling in taste bud cells (TBC). However, factors responsible for this defect remain elusive. Diet rich in saturated fatty acids is known to elicit a metabolic inflammation by promoting intestinal permeation to lipopolysaccharides (LPS), Gram-negative bacteria-derived endotoxins. To determine whether a local inflammation of the gustatory tissue might explain the obese-induced impairment of the oro-sensory detection of lipids, mice were subjected to a DIO protocol. Using a combination of behavioral tests, transcriptomic analyses of gustatory papillae and biochemical assays, we have found that i) DIO elicits a pro-inflammatory genic profile in the circumvallate papillae (CVP), known to house the highest density of lingual taste buds, ii) NFkB, a key player of inflammatory process, might play a role in this transcriptomic pattern, iii) plasma LPS levels are negatively correlated with the preference for oily solution, and iv) a chronic infusion of LPS at a level similar to that found in DIO mice is not sufficient to alter the spontaneous preference for fat in lean mice. Taken together these data bring the demonstration that a saturated high fat diet elicits an inflammatory response at the level of peripheral gustatory pathway and a LPS-induced low-grade endotoxemia alone does not explain the change in the preference for dietary lipids observed in DIO mice.

Highlights

Recent literature highlighted that food-induced obesity is associated with a dysfunction of the gustatory pathway promoting harmful food choices for health both in human and rodents [1e3].Abbreviations: CVP, circumvallate papillae; DIO, diet-induced obesity; HFD, high fat diet; IPA, Ingenuity Pathway Analysis; LPS, lipopolysaccharides; NAc, nucleus accumbens; TBC, taste bud cells; Toll-like receptors (TLR), Toll-like receptor.Please cite this article in press as: A
To determine whether the lower lipid preference observed in the high fat diet (HFD) fed mice could be partly explained by a functional impairment of the gustatory peripheral system, comparison of the transcriptional activities of CVP freshly isolated from lean and DIO mice were undertaken using micro-arrays
Using a whole transcriptomic gene profiling and bioinformatics analysis, we found that the chronic saturated high-fat feeding triggers a proinflammatory transcriptomic pattern in the CVP, as recently reported in the NAc, a brain area involved in the food sensation [8]

Summary

Introduction

Recent literature highlighted that food-induced obesity is associated with a dysfunction of the gustatory pathway promoting harmful food choices for health both in human and rodents [1e3].Please cite this article in press as: A. A. Bernard et al / Biochimie xxx (2018) 1e10 rise in the dopaminergic activity in brain areas responsible for the reward pathway (e.g. NAc), independently of any ingestion [7]. Mice chronically fed a diet high in saturated fat develop NFкB-mediated inflammatory responses in the NAc [8]. This phenomenon might lead to eating behavior impairments since diet-induced obesity (DIO) rats display a progressively worsening deficit of neural reward responses consecutively to a down-regulation of striatal dopamine D2 receptors [9]

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