Insulin signaling in the central nervous system (CNS) regulates energy balance and peripheral
glucose homeostasis. Rictor is a key regulatory/structural subunit of the
mTORC2 complex and is required for hydrophobic motif site phosphorylation of Akt at
serine 473. To examine the contribution of neuronal Rictor/
mTORC2 signaling to CNS regulation of energy and
glucose homeostasis, we utilized Cre-LoxP technology to generate mice lacking Rictor in all neurons, or in either
POMC or AgRP expressing neurons. Rictor deletion in all neurons led to increased fat mass and adiposity,
glucose intolerance and behavioral
leptin resistance. Disrupting Rictor in
POMC neurons also caused
obesity and
hyperphagia, fasting
hyperglycemia and pronounced
glucose intolerance. AgRP neuron specific deletion did not impact energy balance but led to mild
glucose intolerance. Collectively, we show that Rictor/
mTORC2 signaling, especially in
POMC-expressing neurons, is important for central regulation of energy and
glucose homeostasis.