Journal article

Intranasal Targeting of Hypothalamic PTP1B and TCPTP Reinstates Leptin and Insulin Sensitivity and Promotes Weight Loss in Obesity

Garron T Dodd, Chrysovalantou E Xirouchaki, Matthew Eramo, Christina A Mitchell, Zane B Andrews, Belinda A Henry, Michael A Cowley, Tony Tiganis

CELL REPORTS | CELL PRESS | Published : 2019

Abstract

The importance of hypothalamic leptin and insulin resistance in the development and maintenance of obesity remains unclear. The tyrosine phosphatases protein tyrosine phosphatase 1B (PTP1B) and T cell protein tyrosine phosphatase (TCPTP) attenuate leptin and insulin signaling and are elevated in the hypothalami of obese mice. We report that elevated PTP1B and TCPTP antagonize hypothalamic leptin and insulin signaling and contribute to the maintenance of obesity. Deletion of PTP1B and TCPTP in the hypothalami of obese mice enhances CNS leptin and insulin sensitivity, represses feeding, and increases browning, to decrease adiposity and improve glucose metabolism. The daily intranasal administr..

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