Mechanism of leptin action on sleep-wake control.
PI/Investigator: Paige Beck, M.D./Ph.D. Graduate Student; E. Garcia-Rill, COBRE PI, Advisor.
Institution: Center for Translational Neuroscience (COBRE), Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR
Background: Leptin, a hormone that regulates appetite and energy expenditure, is increased in obese individuals, although these individuals often exhibit leptin resistance. Obesity is characterized by a number of sleep/wake disturbances, but the mechanism of leptin action on sleep-wake centers was unknown.
Advance: We discovered that leptin decreases sodium and Ih currents by ~40% in pedunculopontine neurons that modulate waking and REM sleep, thus accounting for its soporific effects. In addition, we determined that these effects are leptin receptor- and G protein-dependent.
Support: F30 HL 108429 NRSA, and Core Facilities provided by COBRE award P20 GM104325.
Public Health Impact: These discoveries identified the membrane and intracellular mechanisms behind leptin effects on sleep/wake control neurons. This information is essential to determining the mechanism behind leptin resistance and the sleep dysregulation in obesity.
Citation and links:
Beck, P., Urbano, F.J., Williams, K.D., and Garcia-Rill, E. 2013 Effects of leptin on pedunculopontine nucleus (PPN) neurons. J Neural Transm 120: 1027-1038. PMID:23263542. PMCID: PMC3618992.
Beck, P., Mahaffey, S., Urbano, F.J., and Garcia-Rill, E. 2013 Role of G-proteins in the effects of leptin on pedunculopontine nucleus (PPN). J Neurochem 126: 705-714. PMID:23692342. PMCID: PMC3766503.