Insulin controls food intake and energy balance via NPY neurons

• DOI: 10.1016/j.molmet.2017.03.013
• Publication Date: 2017-04-12T19:00:34Z
• Authors: Kim Loh; Lei Zhang; Amanda Brandon; Qiaoping Wang; Denovan Begg; Yue Qi; Melissa Fu; Rishikesh Kulkarni; Jonathan Teo; Paul Baldock; Jens C. Brüning; Gregory Cooney; Greg Neely; Herbert Herzog
• Keywords: Male; 570; 1.1 Normal biological development and functioning; Hypothalamus; 610; NPY; 3101 Biochemistry and Cell Biology; Inbred C57BL; Brief Communication; anzsrc-for: 0606 Physiology; Eating; Mice; 03 medical and health sciences; 2.1 Biological and endogenous factors; Animals; Insulin; Neuropeptide Y; Obesity; anzsrc-for: 31 Biological Sciences; Internal medicine; Metabolic and endocrine; Nutrition; Neurons; 2. Zero hunger; 0303 health sciences; Diabetes; anzsrc-for: 3101 Biochemistry and Cell Biology; Neurosciences; Brain; RC31-1245; Mice, Inbred C57BL; anzsrc-for: 0601 Biochemistry and Cell Biology; 7 Affordable and Clean Energy; Drosophila; Energy Metabolism; 31 Biological Sciences

Insulin signaling in the brain has been implicated in the control of satiety, glucose homeostasis and energy balance. However, insulin signaling is dispensable in energy homeostasis controlling AgRP or POMC neurons and it is unclear which other neurons regulate these effects. Here we describe an ancient insulin/NPY neuronal network that governs energy homeostasis across phyla.To address the role of insulin action specifically in NPY neurons, we generated a variety of models by selectively removing insulin signaling in NPY neurons in flies and mice and testing the consequences on energy homeostasis.By specifically targeting the insulin receptor in both fly and mouse NPY expressing neurons, we found NPY-specific insulin signaling controls food intake and energy expenditure, and lack of insulin signaling in NPY neurons leads to increased energy stores and an obese phenotype. Additionally, the lack of insulin signaling in NPY neurons leads to a dysregulation of GH/IGF-1 axis and to altered insulin sensitivity.Taken together, these results suggest that insulin actions in NPY neurons is critical for maintaining energy balance and an impairment of this pathway may be causally linked to the development of metabolic diseases.