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Sun J, Gao Y, Yao T, et al. Adiponectin potentiates the acute effects of leptin in arcuate Pomc neurons. Mol Metab. 2016;5(10):882-891doi: 10.1016/j.molmet.2016.08.007.
Sun, J., Gao, Y., Yao, T., Huang, Y., He, Z., Kong, X., Yu, K. J., Wang, R. T., Guo, H., Yan, J., Chang, Y., Chen, H., Scherer, P. E., Liu, T., & Williams, K. W. (2016). Adiponectin potentiates the acute effects of leptin in arcuate Pomc neurons. Molecular metabolism, 5(10), 882-891. https://doi.org/10.1016/j.molmet.2016.08.007
Sun, Jia, et al. "Adiponectin potentiates the acute effects of leptin in arcuate Pomc neurons." Molecular metabolism vol. 5,10 (2016): 882-891. doi: https://doi.org/10.1016/j.molmet.2016.08.007
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. Adiponectin potentiates the acute effects of leptin in arcuate Pomc neurons. Mol Metab. 2016 Aug 18;5(10):882-891. doi: 10.1016/j.molmet.2016.08.007. eCollection 2016 Oct. PMID: 27689001; PMCID: PMC5034606.
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Mol Metab. 2016 Aug 18;5(10):882-891. doi: 10.1016/j.molmet.2016.08.007. eCollection 2016 Oct.

Adiponectin potentiates the acute effects of leptin in arcuate Pomc neurons.

Molecular metabolism

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

Affiliations

  1. Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, China; Division of Hypothalamic Research, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
  2. National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Division of Hypothalamic Research, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
  3. Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China; Division of Hypothalamic Research, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
  4. Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China; Division of Hypothalamic Research, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
  5. Division of Endocrinology, Beth Israel Deaconess Medical Center and Harvard Medical School, Harvard University, Boston, MA, 02115, USA.
  6. Department of Intensive Care Unit, The Third Affiliated Hospital, Harbin Medical University, No. 150 Haping St, Nangang District, Harbin, 150081, China.
  7. Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
  8. Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China.
  9. National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  10. Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
  11. Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, 75390, USA.
  12. Department of Intensive Care Unit, The Third Affiliated Hospital, Harbin Medical University, No. 150 Haping St, Nangang District, Harbin, 150081, China; Division of Hypothalamic Research, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
  13. Division of Hypothalamic Research, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA. Electronic address: [email protected].

PMID: 27689001 PMCID: PMC5034606 DOI: 10.1016/j.molmet.2016.08.007

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

References

  1. Cell Metab. 2007 Jun;5(6):438-49 - PubMed
  2. Nat Med. 2004 May;10(5):524-9 - PubMed
  3. Obes Rev. 2007 Jan;8(1):21-34 - PubMed
  4. Neuron. 1999 Aug;23 (4):775-86 - PubMed
  5. Am J Physiol Regul Integr Comp Physiol. 2005 Jul;289(1):R247-58 - PubMed
  6. J Clin Invest. 2008 May;118(5):1796-805 - PubMed
  7. Neurosci Lett. 1980 May 1;17(3):307-12 - PubMed
  8. J Biol Chem. 2003 Jan 24;278(4):2461-8 - PubMed
  9. Endocrinology. 2009 Feb;150(2):832-40 - PubMed
  10. J Neurosci. 2009 May 27;29(21):7015-22 - PubMed
  11. Nat Med. 2006 May;12 (5):534-40 - PubMed
  12. FASEB J. 2010 Nov;24(11):4229-39 - PubMed
  13. Cell Metab. 2013 May 7;17(5):790-7 - PubMed
  14. Endocrinology. 2007 Apr;148(4):1868-81 - PubMed
  15. J Biol Chem. 2003 Nov 7;278(45):45021-6 - PubMed
  16. Cell Metab. 2014 Mar 4;19(3):527-38 - PubMed
  17. Neuron. 2011 Aug 11;71(3):488-97 - PubMed
  18. Cell Metab. 2014 Sep 2;20(3):471-82 - PubMed
  19. J Neurosci. 2010 Feb 17;30(7):2472-9 - PubMed
  20. Cell. 2011 Sep 16;146(6):992-1003 - PubMed
  21. Nat Neurosci. 2011 Mar;14(3):351-5 - PubMed
  22. Dis Mon. 1990 Dec;36(12):641-731 - PubMed
  23. Neuron. 1998 Dec;21(6):1375-85 - PubMed
  24. Biochimie. 2012 Oct;94(10):2069-74 - PubMed
  25. Mol Metab. 2013 Oct 23;3(1):19-28 - PubMed
  26. J Endocrinol. 2009 Jan;200(1):93-105 - PubMed
  27. Nat Med. 2011 Jan;17(1):55-63 - PubMed
  28. Nat Neurosci. 2004 May;7(5):493-4 - PubMed
  29. Life Sci. 2005 Jul 29;77(11):1273-82 - PubMed
  30. Ann N Y Acad Sci. 2011 Dec;1243:1-14 - PubMed
  31. J Comp Neurol. 1995 Aug 7;358(4):518-30 - PubMed
  32. Cell Metab. 2013 Jun 4;17 (6):901-15 - PubMed
  33. Nature. 2015 Mar 5;519(7541):45-50 - PubMed
  34. FEBS Lett. 2008 Apr 30;582(10):1471-6 - PubMed
  35. J Clin Invest. 2007 Sep;117(9):2621-37 - PubMed
  36. Diabetes. 1997 Mar;46(3):335-41 - PubMed
  37. Endocrinology. 2009 Nov;150(11):4874-82 - PubMed
  38. J Neurosci. 2010 Jan 27;30(4):1560-5 - PubMed
  39. Nat Med. 2007 Mar;13(3):332-9 - PubMed
  40. Peptides. 2006 Apr;27(4):911-6 - PubMed
  41. Nature. 2007 Sep 13;449(7159):228-32 - PubMed
  42. Brain Res. 2010 May 12;1330:72-82 - PubMed
  43. J Neurosci. 2013 Feb 20;33(8):3624-32 - PubMed
  44. J Biol Chem. 2004 Jan 9;279(2):1304-9 - PubMed
  45. J Neuroendocrinol. 2001 Nov;13(11):959-66 - PubMed
  46. Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14217-22 - PubMed
  47. Diabetes. 2006 Jan;55(1):141-7 - PubMed
  48. J Neurosci. 1994 Aug;14(8):5068-76 - PubMed
  49. J Clin Invest. 2007 Aug;117(8):2325-36 - PubMed
  50. Trends Endocrinol Metab. 2002 Mar;13(2):84-9 - PubMed
  51. Cell Metab. 2007 Jul;6(1):55-68 - PubMed
  52. J Physiol. 2007 Dec 15;585(Pt 3):805-16 - PubMed
  53. Biochem Biophys Res Commun. 2005 Jun 24;332(1):200-5 - PubMed
  54. Islets. 2010 May-Jun;2(3):156-63 - PubMed
  55. Diabetologia. 2007 Mar;50(3):634-42 - PubMed

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