CNS-targets in control of energy and glucose homeostasis.
The exceeding efforts in understanding the signals initiated by nutrients and hormones in the central nervous system (CNS) to regulate glucose and energy homeostasis have largely revolutionized our understanding of the neurocircuitry in control of peripheral metabolism. The ability of neurons to sense nutrients and hormones and to adopt a coordinated response to these signals is of crucial importance in controlling food intake, energy expenditure, glucose and lipid metabolism. Anatomical lesion experiments, pharmacological inhibition of signaling pathways, and, more recently, the analysis of conditional mouse mutants with modifications of hormone and nutrient signaling in defined neuronal populations have broadened our understanding of these complex neurocircuits. This review summarizes recent findings regarding the role of the CNS in sensing and transmitting nutritional and hormonal signals to control energy and glucose homeostasis and aims to define them as potential novel drug targets for the treatment of obesity and type 2 diabetes mellitus.
Kleinridders
André
A
Department of Mouse Genetics and Metabolism, Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD), Center of Molecular Medicine Cologne (CMMC), University of Cologne, 2nd Department for Internal Medicine, University Hospital Cologne, and Max Planck Institute for the Biology of Ageing, Cologne, Germany.
Könner
A Christine
AC
Brüning
Jens C
JC
D000818:Animals; D001835:Body Weight / Q000502:physiology; D002490:Central Nervous System / Q000378:metabolism / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D004734:Energy Metabolism / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D008959:Models, Neurological; D009434:Neural Pathways / Q000378:metabolism / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000502:physiology; D009765:Obesity / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D018377:Neurotransmitter Agents; D005947:Glucose