Western diet, obesity and bariatric surgery sequentially modulated anxiety, eating patterns and brain responses to sucrose in adult Yucatan minipigs

Yentl Gautier,Romain Moirand,Mathilde Mahérault,Noémie Réthoré,Charles-Henri Malbert,Yann Serrand,Damien Bergeat,David Val-Laillet,Paul Meurice,Nicolas Coquery

doi:10.1038/s41598-020-76910-9

Abstract

Palatable sweet/fatty foods overconsumption is a major risk factor for obesity and eating disorders, also having an impact on neuro-behavioural hedonic and cognitive components comparable to what is described for substance abuse. We hypothesized that Yucatan minipigs would show hedonic, cognitive, and affective neuro-behavioral shifts when subjected to western diet (WD) exposure without weight gain, after the onset of obesity, and finally after weight loss induced by caloric restriction with (RYGB) or without (Sham) gastric bypass. Eating behavior, cognitive and affective abilities were assessed with a spatial discrimination task (holeboard test) and two-choice feed tests. Brain responses to oral sucrose were mapped using 18F-FDG positron emission tomography. WD exposure impaired working memory and led to an “addiction-type” neuronal pattern involving hippocampal and cortical brain areas. Obesity induced anxiety-like behavior, loss of motivation, and snacking-type eating behavior. Weight loss interventions normalized the motivational and affective states but not eating behavior patterns. Brain glucose metabolism increased in gustatory (insula) and executive control (aPFC) areas after weight loss, but RYGB showed higher responses in inhibition-related areas (dorsal striatum). These results showed that diet quality, weight loss, and the type of weight loss intervention differently impacted brain responses to sucrose in the Yucatan minipig model.

Highlights

Abreviations aPFC anterior prefrontal cortex BA Brodmann areas Cau caudate nucleus dorsal Anterior Cingulate Cortex (dACC) dorsal anterior cingulate cortex dlPFC dorsolateral prefrontal cortex dpCC dorsal posterior cingulate cortex Fx fornix GP globus pallidus HFS high-fat-sucrose feed Hpc hippocampus high-sucrose feed (HS) high sucrose Interv Intervention (RYGB and Sham pooled together) Ins insula low-sucrose feed (LS) low sucrose Nac nucleus accumbens
Animals were provided with an isocaloric amount of a standard diet (SD) or a high-fat-sucrose Western-type diet (WD) during 8 weeks prior to start the tests, and continued with their respective diets throughout the testing period
When fed ad libitum with high-fat-sucrose feed, western diet (WD) animals from Study 1 (N = 20) increased their feed intake to reach a maximum average of 23.4 ± 0.4 MJ/day the first month of obesogenic challenge

Summary

Introduction

Abreviations aPFC anterior prefrontal cortex BA Brodmann areas Cau caudate nucleus dACC dorsal anterior cingulate cortex dlPFC dorsolateral prefrontal cortex dpCC dorsal posterior cingulate cortex Fx fornix GP globus pallidus HFS high-fat-sucrose feed Hpc hippocampus HS high sucrose Interv Intervention (RYGB and Sham pooled together) Ins insula LS low sucrose Nac nucleus accumbens. The RYGB drastically modifies eating behavior and leads to a generally rapid weight loss compared with a caloric restriction (dieting). It induces profound brain anatomical and functional changes[11,12,13], which could be a reverse switch compared to that observed during weight gain and the introduction of habitual consumption of palatable foods. We present the first complete longitudinal study in adolescent minipigs assessing whether neuro-behavioral responses are impacted by i) chronic consumption of Western-type food without any weight gain (Study 1), ii) weight gain until obesity (Study 2), and iii) weight loss induced by a Roux-en-Y by-pass or restrictive diet (Study 3)

Methods

Results

Discussion

Conclusion