Obese inducing brain mechanism
The research group of Professor Masaharu Noda, Associate Professor Takafumi Shintani, and a graduate student Satoru Higashi of the National Institute for Basic Biology (NIBB) demonstrated that protein tyrosine phosphatase receptor type J (PTPRJ) inhibits leptin signaling and that induction of PTPRJ in the hypothalamus is a cause of leptin resistance. They showed that Ptprj is expressed in hypothalamic neurons together with leptin receptors, and that PTPRJ inhibits activation of the leptin receptor through dephosphorylation of JAK2, a protein tyrosine kinase associated with the leptin receptor. Ptprj-deficient (Ptprj-KO) mice showed no growth retardation, but exhibited lower weight gain, because of a lower food intake and a lower adiposity, than wild-type (WT) mice. Importantly, PTPRJ expression in the hypothalamus was up-regulated by diet-induced obesity, and, thus, diet-induced leptin resistance did not occur in Ptprj-KO mice. Furthermore, the overexpression of PTPRJ in the hypot...