Integration of endocannabinoid and leptin signaling in an appetite-related neural circuit

Young-Hwan Jo, Ying Jiun J Chen, Streamson C. Chua, Jr., David A. Talmage, Lorna W. Role

Research output: Contribution to journalArticle

168 Citations (Scopus)

Abstract

Recently developed therapeutics for obesity, targeted against cannabinoid receptors, result in decreased appetite and sustained weight loss. Prior studies have demonstrated CB1 receptors (CB1Rs) and leptin modulation of cannabinoid synthesis in hypothalamic neurons. Here, we show that depolarization of perifornical lateral hypothalamus (LH) neurons elicits a CB1R-mediated suppression of inhibition in local circuits thought to be involved in appetite and "natural reward." The depolarization-induced decrease in inhibitory tone to LH neurons is blocked by leptin. Leptin inhibits voltage-gated calcium channels in LH neurons via the activation of janus kinase 2 (JAK2) and of mitogen-activated protein kinase (MAPK). Leptin-deficient mice are characterized by both an increase in steady-state voltage-gated calcium currents in LH neurons and a CB1R-mediated depolarization-induced suppression of inhibition that is 6-fold longer than that in littermate controls. Our data provide direct electrophysiological support for the involvement of endocannabinoids and leptin as modulators of hypothalamic circuits underlying motivational aspects of feeding behavior.

Original languageEnglish (US)
Pages (from-to)1055-1066
Number of pages12
JournalNeuron
Volume48
Issue number6
DOIs
StatePublished - Dec 22 2005

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Endocannabinoids
Lateral Hypothalamic Area
Appetite
Leptin
Cannabinoid Receptor CB1
Neurons
Janus Kinase 2
Cannabinoid Receptors
Cannabinoids
Feeding Behavior
Calcium Channels
Mitogen-Activated Protein Kinases
Reward
Weight Loss
Obesity
Calcium

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Integration of endocannabinoid and leptin signaling in an appetite-related neural circuit. / Jo, Young-Hwan; Chen, Ying Jiun J; Chua, Jr., Streamson C.; Talmage, David A.; Role, Lorna W.

In: Neuron, Vol. 48, No. 6, 22.12.2005, p. 1055-1066.

Research output: Contribution to journalArticle

Jo, Young-Hwan ; Chen, Ying Jiun J ; Chua, Jr., Streamson C. ; Talmage, David A. ; Role, Lorna W. / Integration of endocannabinoid and leptin signaling in an appetite-related neural circuit. In: Neuron. 2005 ; Vol. 48, No. 6. pp. 1055-1066.
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