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About the Authors:
Jae Hoon Jeong
Roles Formal analysis, Investigation
Affiliation: Division of Endocrinology, Department of Medicine, Albert Einstein College of Medicine, New York, United States of America
Dong Kun Lee
Roles Formal analysis, Investigation
Affiliations Division of Endocrinology, Department of Medicine, Albert Einstein College of Medicine, New York, United States of America, Department of Physiology, College of Medicine, Gyeongsang National University, Jinju, Korea
Shun-Mei Liu
Roles Investigation
Affiliation: Division of Endocrinology, Department of Medicine, Albert Einstein College of Medicine, New York, United States of America
Streamson C. Chua Jr.
Roles Conceptualization, Methodology, Writing - review & editing
Affiliation: Division of Endocrinology, Department of Medicine, Albert Einstein College of Medicine, New York, United States of America
Gary J. Schwartz
Roles Conceptualization, Methodology, Writing - review & editing
Affiliation: Division of Endocrinology, Department of Medicine, Albert Einstein College of Medicine, New York, United States of America
Young-Hwan Jo
Roles Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Supervision, Writing - original draft, Writing - review & editing
* E-mail: [email protected]
Affiliations Division of Endocrinology, Department of Medicine, Albert Einstein College of Medicine, New York, United States of America, Department of Molecular Pharmacology, Albert Einstein College of Medicine, New York, United States of America
ORCID http://orcid.org/0000-0001-6939-8000Abstract
Proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARC) respond to numerous hormonal and neural signals, resulting in changes in food intake. Here, we demonstrate that ARC POMC neurons express capsaicin-sensitive transient receptor potential vanilloid 1 receptor (TRPV1)-like receptors. To show expression of TRPV1-like receptors in ARC POMC neurons, we use single-cell reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, electrophysiology, TRPV1 knock-out (KO), and TRPV1-Cre knock-in mice. A small elevation of temperature in the physiological range is enough to depolarize ARC POMC neurons. This depolarization is blocked by the TRPV1 receptor antagonist and by Trpv1 gene knockdown. Capsaicin-induced activation reduces food intake that is abolished by a melanocortin receptor antagonist. To selectively stimulate TRPV1-like receptor-expressing ARC POMC neurons in the ARC, we generate an adeno-associated virus serotype 5 (AAV5) carrying a Cre-dependent channelrhodopsin-2 (ChR2)-enhanced yellow fluorescent protein (eYFP) expression cassette under the control of the two neuronal POMC enhancers (nPEs). Optogenetic stimulation of TRPV1-like receptor-expressing POMC neurons decreases food intake. Hypothalamic temperature is rapidly elevated and reaches to approximately 39 °C...