Obesity-induced hyperglycemia impairs oral tolerance induction and aggravates food allergy.

Obesity and type 2 diabetes (T2D) have been found to be associated with abnormalities in several organs, including the intestine. These conditions can lead to changes in gut homeostasis, compromising tolerance to luminal antigens and increasing susceptibility to food allergies. The underlying mechanisms for this phenomenon are not yet fully understood. In this study, we investigated changes in the intestinal mucosa of diet-induced obese mice and found that they exhibited increased gut permeability and reduced Treg cells frequency. Upon oral treatment with ovalbumin (OVA), obese mice failed to develop oral tolerance. However, hyperglycemia treatment improved intestinal permeability and oral tolerance induction in mice. Furthermore, we observed that obese mice exhibited a more severe food allergy to OVA, and this allergy was alleviated after treatment with a hypoglycemic drug. Importantly, our findings were translated to obese humans. Individuals with T2D had higher serum IgE levels and downregulated genes related to gut homeostasis. Taken together, our results suggest that obesity-induced hyperglycemia can lead to a failure in oral tolerance and to exacerbation of food allergy. These findings shed light on the mechanisms underlying the relationship among obesity, T2D, and gut mucosal immunity, which could inform the development of new therapeutic approaches.

High-fat diet withdrawal modifies alcohol preference and transcription of dopaminergic and GABAergic receptors.

The bidirectional and positive relation between the ingestion of fat and alcohol has become the subject of extensive discussion. However, this relation is more studied in animal models of binge eating with intermittent access of high-fat diet or in a model of short period of this diet consumption. Here, we developed a model to elucidate how chronic high-fat diet and its withdrawal influence alcohol intake (two-bottle choice) and anxiety behavior (marble burying test). In the first experimental stage, animals were fed on standard (AIN93G) or high sugar and butter (HSB) diet for 8 weeks. Then, a protocol of free-choice between water and a 10% alcohol solution was introduced, and the HSB diet was replaced with AIN93G in two experimental groups. The result obtained with this model point out that the relation among high-fat diet consumption and alcohol intake appears to depend on the presence or absence of the diet when alcohol intake is evaluated, and that an imbalance in the mesocorticolimbic dopaminergic pathway, observed by the transcriptional regulation of the dopamine receptors (Drd1/Drd2) and GABAB receptors subunit (Gabbr1/Gabbr2), can be driving the alcohol intake.