Abstract
Energy homeostasis is tightly regulated by the central nervous system which responds to nervous and circulating inputs to adapt food intake and energy expenditure. However, the rewarding and motivational aspect of food is tightly dependent of dopamine (DA) release in mesocorticolimbic (MCL) system and could be operant in uncontrolled caloric intake and obesity. Accumulating evidence indicate that manipulating the microbiota–gut–brain axis through prebiotic supplementation can have beneficial impact of the host appetite and body weight. However, the consequences of manipulating the implication of the microbiota–gut–brain axis in the control motivational and hedonic/reinforcing aspects of food are still underexplored. In this study, we investigate whether and how dietary prebiotic fructo-oligosaccharides (FOS) could oppose, or revert, the change in hedonic and homeostatic control of feeding occurring after a 2-months exposure to high-fat high-sugar (HFHS) diet. The reinforcing and motivational components of food reward were assessed using a two-food choice paradigm and a food operant behavioral test in mice exposed to FOS either during or after HFHS exposure. We also performed mRNA expression analysis for key genes involved in limbic and hypothalamic control of feeding. We show in a preventive-like approach, FOS addition of HFHS diet had beneficial impact of hypothalamic neuropeptides, and decreased the operant performance for food but only after an overnight fast while it did not prevent the imbalance in mesolimbic markers for DA signaling induced by palatable diet exposure nor the spontaneous tropism for palatable food when given the choice. However, when FOS was added to control diet after chronic HFHS exposure, although it did not significantly alter body weight loss, it greatly decreased palatable food tropism and consumption and was associated with normalization of MCL markers for DA signaling. We conclude that the nature of the diet (regular chow or HFHS) as well as the timing at which prebiotic supplementation is introduced (preventive or curative) greatly influence the efficacy of the gut–microbiota–brain axis. This crosstalk selectively alters the hedonic or motivational drive to eat and triggers molecular changes in neural substrates involved in the homeostatic and non-homeostatic control of body weight.
Highlights
Obesity and corollary pathologies, such as dyslipidemia, diabetes, and cardiovascular diseases are spreading in both developed and developing countries as a result of increased accessibility to energy-dense food associated with a general decrease in physical activity and energy expenditure [1]
An additional two animal cohorts were dedicated to explore the corrective potency of prebiotic supplementation onto metabolic and behavioral changes induced by a 2 months exposure to high-fat high-sugar (HFHS) diet
While average body weight did not differ among groups before the treatment, a significant increase in body weight was reached after HFHS but not HFHS-FOS exposure (Figures 1B,E,H)
Summary
Obesity and corollary pathologies, such as dyslipidemia, diabetes, and cardiovascular diseases are spreading in both developed and developing countries as a result of increased accessibility to energy-dense food associated with a general decrease in physical activity and energy expenditure [1]. The rewarding aspects of energy-dense food largely depends on dopamine (DA) release from dopaminergic neurons in the ventral tegmental area that project to limbic regions, notably the prefrontal cortex and the nucleus accumbens (NAcc) [4, 5]. This neural substrate referred as to mesolimbic “reward” circuit is instrumental in the encoding of both the volume of desire, i.e., “motivation” and the hedonic aspect, i.e., “liking” in food rewards [6]
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