The Tryptophan/Kynurenine Pathway: A Novel Cross-Talk between Nutritional Obesity, Bariatric Surgery and Taste of Fat.

Arnaud Bernard,Aurélie Dastugue,Claire Blanchard,Pascaline Delaby,Jean-Paul Pais De Barros,Séverine Ledoux,Audrey Ayer,Jean-Charles Martin,Philippe Besnard,Cindy Le Bourgot,Cédric Le May

doi:10.3390/nu13041366

Abstract

Diet-induced obesity (DIO) reduces the orosensory perception of lipids in rodents and in some humans. Although bariatric surgery partially corrects this alteration, underlying mechanisms remain poorly understood. To explore whether metabolic changes might explain this fat taste disturbance, plasma metabolome analyses, two-bottle choice tests and fungiform papillae (Fun) counting were performed in vertical sleeve gastrectomized (VSG) mice and sham-operated controls. An exploratory clinic study was also carried out in adult patients undergone a VSG. In mice, we found that (i) the VSG reduces both the plasma neurotoxic signature due to the tryptophan/kynurenine (Trp/Kyn) pathway overactivation and the failure of fat preference found in sham-operated DIO mice, (ii) the activity of Trp/Kyn pathway is negatively correlated to the density of Fun, and (iii) the pharmacological inhibition of the Kyn synthesis mimics in non-operated DIO mice the positive effects of VSG (i.e., decrease of Kyn synthesis, increase of Fun number, improvement of the fat taste perception). In humans, a reduction of the plasma Kyn level is only found in patients displaying a post-surgery improvement of their fat taste sensitivity. Altogether these data provide a plausible metabolic explanation to the degradation of the orosensory lipid perception observed in obesity.

Highlights

vertical sleeve gastrectomized (VSG) Reduces the Metabolic Dysfunctions Found in diet-induced obese (DIO) Mice
These metabolic improvements correlated with the evolution of body mass, which increased in the sham-DIO group but decreased in the VSG-DIO mice despite still being fed with the high fat diet (HFD) (Figure 1C)
Mechanisms by which the fat taste sensitivity is altered in DIO rodents, and is improved after bariatric surgery are not yet fully known

Summary

Introduction

Recent studies suggest that the sense of taste might be compromised in obesity contributing to unhealthy food choices [1]. By providing critical information about the nature and quality of foods, gustation contributes to the decision to eat. This taste-guided ingestive behavior requires the chemo-detection of tastants by gustatory papillae mainly found in the lingual epithelium, followed by the integration of generated taste signals by specific brain structures including areas responsible for the food reward [2]. In addition to the primary tastes (i.e., sweet, bitter, salty, sour and umami), a growing number of studies pleads in favor of a sixth taste modality responsible for the perception of dietary lipids [3,4,5]. Rats hypo-responsive to fatty acid stimuli preferentially consume high fat diet (HFD), likely to reach a hedonic satisfaction, and become obese [8]

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Results

Conclusion