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
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..View full abstract
Awarded by National Health and Medical Research Council (NHMRC) of Australia
This work was supported by a grant from the National Health and Medical Research Council (NHMRC) of Australia to T.T. (1100240). T.T. (1103037), M.A.C. (1079422), and Z.B.A. (1154974) are NHMRC Research Fellows.