Hosted by the Wellcome Neural Dynamics PhD Programme
Obesity is associated with substantially increased risk for neurodegenerative and neuropsychiatric disorders, including anxiety and depression. The mechanistic link for the relationship between obesity and neuropsychiatric disorders, however, is unknown. In 2016, our lab discovered asprosin, a fasting-induced hormone that is highly expressed in adipose tissue. Upon secretion, asprosin stimulates appetite and hepatic glucose release. Asprosin is a ~30 kDa C-terminal cleavage product of fibrillin-1 that normally circulates in cerebrospinal fluid (CSF) and plasma at nanomolar levels, and is significantly elevated in obesity. Importantly, we have demonstrated that anti-asprosin monoclonal antibodies (mAbs) are a dual-effect pharmacologic therapy that targets the two key pillars of metabolic syndrome (MS) – overnutrition and blood glucose burden with obesity. Recently we have also identified the neural target for asprosin, Protein tyrosine phosphatase receptor δ (Ptprd), which is highly expressed throughout the brain, in regions that have been implicated in cognition. This study suggests that elevated levels of asprosin alter cognitive functions, thereby providing a potential mechanistic link with obesity and a potential therapy for certain neuropsychiatric disorders. Specifically, my results indicate that (1) pharmacologic asprosin neutralization mitigates cognitive deficits in diet-induced obese mice, (2) asprosin neutralization in lean mice improves cognition in certain assays, despite not affecting metabolism, and (3) genetic inhibition of asprosin and its receptor leads to improvement of cognition. Future studies will delineate the central circuit necessary for asprosin-mediated modulation of neuropsychiatric disorders. My studies thus far suggest a novel function of asprosin in the control of cognition, and that the anti-asprosin mAb could be a novel cognitive agent that may have particularly enhanced benefits for individuals with obesity-associated neuropsychiatric disorders, significantly improving the quality of life in these individuals.
Join online: https://bristol-ac-uk.zoom.us/j/94138286231?pwd=MlRURE1SWjR6OTZCR1Fnak9QbGxhUT09, Meeting ID: 941 3828 6231, Passcode: 277162