Food Reward Alterations during Obesity Are Associated with Inflammation in the Striatum in Mice: Beneficial Effects of Akkermansia muciniphila

Abstract

The reward system involved in hedonic food intake presents neuronal and behavioral dysregulations during obesity. Moreover, gut microbiota dysbiosis during obesity promotes low-grade inflammation in peripheral organs and in the brain contributing to metabolic alterations. The mechanisms underlying reward dysregulations during obesity remain unclear. We investigated if inflammation affects the striatum during obesity using a cohort of control-fed or diet-induced obese (DIO) male mice. We tested the potential effects of specific gut bacteria on the reward system during obesity by administrating Akkermansia muciniphila daily or a placebo to DIO male mice. We showed that dysregulations of the food reward are associated with inflammation and alterations in the blood–brain barrier in the striatum of obese mice. We identified Akkermansia muciniphila as a novel actor able to improve the dysregulated reward behaviors associated with obesity, potentially through a decreased activation of inflammatory pathways and lipid-sensing ability in the striatum. These results open a new field of research and suggest that gut microbes can be considered as an innovative therapeutic approach to attenuate reward alterations in obesity. This study provides substance for further investigations of Akkermansia muciniphila-mediated behavioral improvements in other inflammatory neuropsychiatric disorders.

Reversal of High Fat Diet-Induced Obesity, Systemic Inflammation, and Astrogliosis by the NLRP3 Inflammasome Inhibitors NT-0249 and NT-0796

“…Emerging data suggest that reactive gliosis in the hypothalamus and elsewhere contributes to the maintenance of obesity (Huwart et al, 2022;Sa et al, 2022). In line with this, weightreducing efficacy of NLRP3 inhibition in DIO mice was greatest when NT-0249 or NT-0796 dosing strategies achieved significant brain exposure.…”

Influence of Bariatric Surgery on Gut Microbiota Composition and Its Implication on Brain and Peripheral Targets

“…The influence of Akkermansia on food reward processes has been described in another study, where Akkermansia was administered to diet-induced obese mice [156]. After supplementation, dysregulated reward behaviors were improved through reductions in striatal inflammation and blood-brain barrier permeability [156]. As previously discussed, metabolic endotoxemia secondary to perturbations in microbiota leads to the low-grade systemic inflammation seen in obesity, including neuroinflammation, often through excessive activation and maturation of microglia [82,234].…”

“…Although this study did not include RYGB patients, this surgery also promotes increased Akkermansia, which may confer similar benefits. The influence of Akkermansia on food reward processes has been described in another study, where Akkermansia was administered to diet-induced obese mice [156]. After supplementation, dysregulated reward behaviors were improved through reductions in striatal inflammation and blood-brain barrier permeability [156].…”

Conditioned overconsumption is dependent on reinforcer type in lean, but not obese, mice

“…Lastly, we tested whether DIO mice would be more prone to overconsumption in this task. DIO mice have been tested in Pavlovian and operant training paradigms, and have displayed deficits in motivation and learning, particularly in the progressive ratio task (Cordner & Tamashiro, 2015; Huwart et al, 2022; Kanoski et al, 2007; Sharma et al, 2013). In one notable exception, mice were trained to increase the level of force to obtain food rewards rather than number of operant responses (Matikainen-Ankney et al, 2023).…”