A Hypothalamic Phosphatase Switch Coordinates Energy Expenditure with Feeding
Garron T Dodd, Zane B Andrews, Stephanie E Simonds, Natalie J Michael, Michael DeVeer, Jens C Bruening, David Spanswick, Michael A Cowley, Tony Tiganis
CELL METABOLISM | CELL PRESS | Published : 2017
Beige adipocytes can interconvert between white and brown-like states and switch between energy storage versus expenditure. Here we report that beige adipocyte plasticity is important for feeding-associated changes in energy expenditure and is coordinated by the hypothalamus and the phosphatase TCPTP. A fasting-induced and glucocorticoid-mediated induction of TCPTP, inhibited insulin signaling in AgRP/NPY neurons, repressed the browning of white fat and decreased energy expenditure. Conversely feeding reduced hypothalamic TCPTP, to increase AgRP/NPY neuronal insulin signaling, white adipose tissue browning and energy expenditure. The feeding-induced repression of hypothalamic TCPTP was defec..View full abstract
We thank Sunena Bhandari, Tariq Butt, Florian Wiede, Jihane Homman-Ludiye, and Tara Sepehrizadeh for technical assistance, Matthew Watt for reagents, and Herbert Herzog for access to Insr<SUP>fl/fl</SUP> mice. This work was supported by the NHMRC of Australia (to T.T., Z.B.A., D.S., M.A.C.), the Diabetes Australia Research Trust (to G.T.D.), and the National Imaging Facility (M.D.).