Maternal treatment with oral intestinal alkaline phosphatase mitigates high fat diet-induced cognitive disorders in offspring mice

Abstract

Intestinal alkaline phosphatase (IAP) is an endogenous enzyme that promotes gastrointestinal homeostasis by detoxifying inflammatory mediators, tightening the gut barrier and promoting a healthy microbiome. Oral IAP administration was efficacious in ameliorating diabetes in a high fat diet (HFD)-induced murine model. In humans, maternal obesity and diabetes during pregnancy have been associated with an increased risk of autism spectrum disorders (ASD). In mice, HFD-induced maternal obesity leads to offspring with cognitive deficiency. Here we investigated whether IAP administration to obese dams could ameliorate autism-like disorders in mice. Using a HFD murine model, we recapitulated that maternal obesity leads to male offspring with social deficits as shown by the three chamber test and reciprocal social interaction analyses. Notably, oral delivery of IAP to dams improved those deficiencies. In addition, a jumping behavior was noted in pups from obese dams, which was rescued by maternal IAP treatment. Our findings suggest that maternal treatment with IAP can relieve some ASD-like symptoms in offspring mice.