Assessing the role of PTEN in cholinergic neurons in glucose and energy homeostasis

Insulin resistance and insulin deficiency are key determinants of type 2 diabetes. Insulin resistance is manifested by attenuation of insulin signaling. A major insulin signaling pathway is mediated by phosphatidyl inositol kinase (PI3K), which is negatively regulated by phosphatase and tensin homologue (PTEN). Neuronal PI3K-mediated insulin action plays a critical role in the regulation of systemic insulin resistance. The dorsal ventral complex (DVC) is the control centre of vagal activity and utilizes acetylcholine, a neurotransmitter, which is synthesized by the enzyme choline acetyl transferase (ChAT). To assess the role of PTEN in cholinergic neurons, we generated mice deficient of PTEN in these neurons using the cre-loxP system. These mice were protected against high fat diet-induced weight gain and glucose intolerance. They also had less inflammatory adipose tissue. Overall, PTEN deletion in the cholinergic neurons provides protection against diet-induced obesity and diabetes.M.Sc