Adiponectin potentiates the acute effects of leptin in arcuate Pomc neurons

Jia Sun, Yong Gao, Ting Yao, Yiru Huang, Zhenyan He, Xingxing Kong, Kai jiang Yu, Rui tao Wang, Hongbo Guo, Jianqun Yan, Yongsheng Chang, Hong Chen, Philipp E. Scherer, Tiemin Liu, Kevin W. Williams

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Objective Adiponectin receptors (AdipoRs) are located on neurons of the hypothalamus involved in metabolic regulation – including arcuate proopiomelanocortin (Pomc) and Neuropeptide Y/Agouti-related peptide (NPY/AgRP) neurons. AdipoRs play a critical role in regulating glucose and fatty acid metabolism by initiating several signaling cascades overlapping with Leptin receptors (LepRs). However, the mechanism by which adiponectin regulates cellular activity in the brain remains undefined. Methods In order to resolve this issue, we utilized neuron-specific transgenic mouse models to identify Pomc and NPY/AgRP neurons which express LepRs for patch-clamp electrophysiology experiments. Results We found that leptin and adiponectin synergistically activated melanocortin neurons in the arcuate nucleus. Conversely, NPY/AgRP neurons were inhibited in response to adiponectin. The adiponectin-induced depolarization of arcuate Pomc neurons occurred via activation of Phosphoinositide-3-kinase (PI3K) signaling, independent of 5′ AMP-activated protein kinase (AMPK) activity. Adiponectin also activated melanocortin neurons at various physiological glucose levels. Conclusions Our results demonstrate a requirement for PI3K signaling in the acute adiponectin-induced effects on the cellular activity of arcuate melanocortin neurons. Moreover, these data provide evidence for PI3K as a substrate for both leptin and adiponectin to regulate energy balance and glucose metabolism via melanocortin activity.

Original languageEnglish (US)
Pages (from-to)882-891
Number of pages10
JournalMolecular Metabolism
Volume5
Issue number10
DOIs
StatePublished - Oct 1 2016

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Pro-Opiomelanocortin
Adiponectin
Leptin
Neurons
Melanocortins
1-Phosphatidylinositol 4-Kinase
Neuropeptide Y
Adiponectin Receptors
Leptin Receptors
Glucose
Peptides
Arcuate Nucleus of Hypothalamus
AMP-Activated Protein Kinases
Electrophysiology
Transgenic Mice
Hypothalamus
Fatty Acids

Keywords

  • Diabetes
  • Electrophysiology
  • Energy balance
  • Melanocortin
  • Obesity
  • Patch-clamp

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Adiponectin potentiates the acute effects of leptin in arcuate Pomc neurons. / Sun, Jia; Gao, Yong; Yao, Ting; Huang, Yiru; He, Zhenyan; Kong, Xingxing; Yu, Kai jiang; Wang, Rui tao; Guo, Hongbo; Yan, Jianqun; Chang, Yongsheng; Chen, Hong; Scherer, Philipp E.; Liu, Tiemin; Williams, Kevin W.

In: Molecular Metabolism, Vol. 5, No. 10, 01.10.2016, p. 882-891.

Research output: Contribution to journalArticle

Sun, J, Gao, Y, Yao, T, Huang, Y, He, Z, Kong, X, Yu, KJ, Wang, RT, Guo, H, Yan, J, Chang, Y, Chen, H, Scherer, PE, Liu, T & Williams, KW 2016, 'Adiponectin potentiates the acute effects of leptin in arcuate Pomc neurons', Molecular Metabolism, vol. 5, no. 10, pp. 882-891. https://doi.org/10.1016/j.molmet.2016.08.007
Sun, Jia ; Gao, Yong ; Yao, Ting ; Huang, Yiru ; He, Zhenyan ; Kong, Xingxing ; Yu, Kai jiang ; Wang, Rui tao ; Guo, Hongbo ; Yan, Jianqun ; Chang, Yongsheng ; Chen, Hong ; Scherer, Philipp E. ; Liu, Tiemin ; Williams, Kevin W. / Adiponectin potentiates the acute effects of leptin in arcuate Pomc neurons. In: Molecular Metabolism. 2016 ; Vol. 5, No. 10. pp. 882-891.
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abstract = "Objective Adiponectin receptors (AdipoRs) are located on neurons of the hypothalamus involved in metabolic regulation – including arcuate proopiomelanocortin (Pomc) and Neuropeptide Y/Agouti-related peptide (NPY/AgRP) neurons. AdipoRs play a critical role in regulating glucose and fatty acid metabolism by initiating several signaling cascades overlapping with Leptin receptors (LepRs). However, the mechanism by which adiponectin regulates cellular activity in the brain remains undefined. Methods In order to resolve this issue, we utilized neuron-specific transgenic mouse models to identify Pomc and NPY/AgRP neurons which express LepRs for patch-clamp electrophysiology experiments. Results We found that leptin and adiponectin synergistically activated melanocortin neurons in the arcuate nucleus. Conversely, NPY/AgRP neurons were inhibited in response to adiponectin. The adiponectin-induced depolarization of arcuate Pomc neurons occurred via activation of Phosphoinositide-3-kinase (PI3K) signaling, independent of 5′ AMP-activated protein kinase (AMPK) activity. Adiponectin also activated melanocortin neurons at various physiological glucose levels. Conclusions Our results demonstrate a requirement for PI3K signaling in the acute adiponectin-induced effects on the cellular activity of arcuate melanocortin neurons. Moreover, these data provide evidence for PI3K as a substrate for both leptin and adiponectin to regulate energy balance and glucose metabolism via melanocortin activity.",
keywords = "Diabetes, Electrophysiology, Energy balance, Melanocortin, Obesity, Patch-clamp",
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T1 - Adiponectin potentiates the acute effects of leptin in arcuate Pomc neurons

AU - Sun, Jia

AU - Gao, Yong

AU - Yao, Ting

AU - Huang, Yiru

AU - He, Zhenyan

AU - Kong, Xingxing

AU - Yu, Kai jiang

AU - Wang, Rui tao

AU - Guo, Hongbo

AU - Yan, Jianqun

AU - Chang, Yongsheng

AU - Chen, Hong

AU - Scherer, Philipp E.

AU - Liu, Tiemin

AU - Williams, Kevin W.

PY - 2016/10/1

Y1 - 2016/10/1

N2 - Objective Adiponectin receptors (AdipoRs) are located on neurons of the hypothalamus involved in metabolic regulation – including arcuate proopiomelanocortin (Pomc) and Neuropeptide Y/Agouti-related peptide (NPY/AgRP) neurons. AdipoRs play a critical role in regulating glucose and fatty acid metabolism by initiating several signaling cascades overlapping with Leptin receptors (LepRs). However, the mechanism by which adiponectin regulates cellular activity in the brain remains undefined. Methods In order to resolve this issue, we utilized neuron-specific transgenic mouse models to identify Pomc and NPY/AgRP neurons which express LepRs for patch-clamp electrophysiology experiments. Results We found that leptin and adiponectin synergistically activated melanocortin neurons in the arcuate nucleus. Conversely, NPY/AgRP neurons were inhibited in response to adiponectin. The adiponectin-induced depolarization of arcuate Pomc neurons occurred via activation of Phosphoinositide-3-kinase (PI3K) signaling, independent of 5′ AMP-activated protein kinase (AMPK) activity. Adiponectin also activated melanocortin neurons at various physiological glucose levels. Conclusions Our results demonstrate a requirement for PI3K signaling in the acute adiponectin-induced effects on the cellular activity of arcuate melanocortin neurons. Moreover, these data provide evidence for PI3K as a substrate for both leptin and adiponectin to regulate energy balance and glucose metabolism via melanocortin activity.

AB - Objective Adiponectin receptors (AdipoRs) are located on neurons of the hypothalamus involved in metabolic regulation – including arcuate proopiomelanocortin (Pomc) and Neuropeptide Y/Agouti-related peptide (NPY/AgRP) neurons. AdipoRs play a critical role in regulating glucose and fatty acid metabolism by initiating several signaling cascades overlapping with Leptin receptors (LepRs). However, the mechanism by which adiponectin regulates cellular activity in the brain remains undefined. Methods In order to resolve this issue, we utilized neuron-specific transgenic mouse models to identify Pomc and NPY/AgRP neurons which express LepRs for patch-clamp electrophysiology experiments. Results We found that leptin and adiponectin synergistically activated melanocortin neurons in the arcuate nucleus. Conversely, NPY/AgRP neurons were inhibited in response to adiponectin. The adiponectin-induced depolarization of arcuate Pomc neurons occurred via activation of Phosphoinositide-3-kinase (PI3K) signaling, independent of 5′ AMP-activated protein kinase (AMPK) activity. Adiponectin also activated melanocortin neurons at various physiological glucose levels. Conclusions Our results demonstrate a requirement for PI3K signaling in the acute adiponectin-induced effects on the cellular activity of arcuate melanocortin neurons. Moreover, these data provide evidence for PI3K as a substrate for both leptin and adiponectin to regulate energy balance and glucose metabolism via melanocortin activity.

KW - Diabetes

KW - Electrophysiology

KW - Energy balance

KW - Melanocortin

KW - Obesity

KW - Patch-clamp

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