Adiponectin potentiates the acute effects of leptin in arcuate Pomc neurons.
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.
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.
Jia
J
Sun
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.
Yong
Y
Gao
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.
Ting
T
Yao
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.
Yiru
Y
Huang
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.
Zhenyan
Z
He
Division of Endocrinology, Beth Israel Deaconess Medical Center and Harvard Medical School, Harvard University, Boston, MA, 02115, USA.
Xingxing
X
Kong
Department of Intensive Care Unit, The Third Affiliated Hospital, Harbin Medical University, No. 150 Haping St, Nangang District, Harbin, 150081, China.
Kai-Jiang
KJ
Yu
Department of Intensive Care Unit, The Third Affiliated Hospital, Harbin Medical University, No. 150 Haping St, Nangang District, Harbin, 150081, China.
Rui-Tao
RT
Wang
Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Hongbo
H
Guo
Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China.
Jianqun
J
Yan
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Yongsheng
Y
Chang
Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Hong
H
Chen
Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, 75390, USA.
Philipp E
PE
Scherer
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.
Tiemin
T
Liu
Division of Hypothalamic Research, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA. Electronic address: Kevin.Williams@UTSouthwestern.edu.
Kevin W
KW
Williams
Diabetes; Electrophysiology; Energy balance; Melanocortin; Obesity; Patch-clamp
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