Insulin and leptin excite anorexigenic pro-opiomelanocortin neurones via activation of TRPC5 channels

Research output: Contribution to journalReview article

10 Citations (Scopus)

Abstract

Pro-opiomelanocortin (POMC) neurones within the hypothalamic arcuate nucleus are vital anorexigenic neurones. Both the insulin receptor and leptin receptor are coupled to activation of phosphatidylinositide-3 kinase (PI3K) to regulate multiple functions that increase POMC neuronal excitability. Using whole-cell recording in several mammalian species, we have found that both insulin and leptin depolarised POMC neurones via activation of transient receptor potential (TRPC)5 channels. TRPC5 channels have been rigorously characterised as the downstream effector based on their biophysical properties, pharmacological profile, and localisation by immunocytochemistry and single-cell reverse transcriptase-polymerase chain reaction. By contrast, insulin and leptin hyperpolarise and inhibit neuropeptide Y/agouti-related peptide neurones via activation of KATP channels. As proof of principle, insulin given i.c.v. robustly inhibits food intake and increases O2 utilisation, CO2 production and metabolic heat production. Therefore, these findings indicate that the depolarisation/excitation of POMC neurones by insulin and leptin is preserved across mammalian species and the activation of TRPC5 channels is likely a major mechanism by which insulin and leptin regulate energy homeostasis in mammals.

Original languageEnglish (US)
Article numbere12501
JournalJournal of Neuroendocrinology
Volume30
Issue number2
DOIs
StatePublished - Feb 1 2018

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Pro-Opiomelanocortin
Leptin
Insulin
Neurons
Leptin Receptors
KATP Channels
Arcuate Nucleus of Hypothalamus
Thermogenesis
Neuropeptide Y
Insulin Receptor
Patch-Clamp Techniques
Reverse Transcriptase Polymerase Chain Reaction
Mammals
Homeostasis
Phosphotransferases
Eating
Immunohistochemistry
Pharmacology
Peptides

Keywords

  • insulin
  • leptin
  • POMC neurone
  • TRPC5 channel

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

Cite this

Insulin and leptin excite anorexigenic pro-opiomelanocortin neurones via activation of TRPC5 channels. / Qiu, Jian; Wagner, E. J.; Ronnekleiv, Oline; Kelly, Martin.

In: Journal of Neuroendocrinology, Vol. 30, No. 2, e12501, 01.02.2018.

Research output: Contribution to journalReview article

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AB - Pro-opiomelanocortin (POMC) neurones within the hypothalamic arcuate nucleus are vital anorexigenic neurones. Both the insulin receptor and leptin receptor are coupled to activation of phosphatidylinositide-3 kinase (PI3K) to regulate multiple functions that increase POMC neuronal excitability. Using whole-cell recording in several mammalian species, we have found that both insulin and leptin depolarised POMC neurones via activation of transient receptor potential (TRPC)5 channels. TRPC5 channels have been rigorously characterised as the downstream effector based on their biophysical properties, pharmacological profile, and localisation by immunocytochemistry and single-cell reverse transcriptase-polymerase chain reaction. By contrast, insulin and leptin hyperpolarise and inhibit neuropeptide Y/agouti-related peptide neurones via activation of KATP channels. As proof of principle, insulin given i.c.v. robustly inhibits food intake and increases O2 utilisation, CO2 production and metabolic heat production. Therefore, these findings indicate that the depolarisation/excitation of POMC neurones by insulin and leptin is preserved across mammalian species and the activation of TRPC5 channels is likely a major mechanism by which insulin and leptin regulate energy homeostasis in mammals.

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