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CRFR1 in AgRP Neurons Modulates Sympathetic Nervous System Activity to Adapt to Cold Stress and Fasting.

Abstract：

:Signaling by the corticotropin-releasing factor receptor type 1 (CRFR1) plays an important role in mediating the autonomic response to stressful challenges. Multiple hypothalamic nuclei regulate sympathetic outflow. Although CRFR1 is highly expressed in the arcuate nucleus (Arc) of the hypothalamus, the identity of these neurons and the role of CRFR1 here are presently unknown. Our studies show that nearly half of Arc-CRFR1 neurons coexpress agouti-related peptide (AgRP), half of which originate from POMC precursors. Arc-CRFR1 neurons are innervated by CRF neurons in the hypothalamic paraventricular nucleus, and CRF application decreases AgRP(+)CRFR1(+) neurons' excitability. Despite similar anatomy in both sexes, only female mice selectively lacking CRFR1 in AgRP neurons showed a maladaptive thermogenic response to cold and reduced hepatic glucose production during fasting. Thus, CRFR1, in a subset of AgRP neurons, plays a regulatory role that enables appropriate sympathetic nervous system activation and consequently protects the organism from hypothermia and hypoglycemia.

journal_name

Cell Metab

journal_title

Cell metabolism

authors

Kuperman Y,Weiss M,Dine J,Staikin K,Golani O,Ramot A,Nahum T,Kühne C,Shemesh Y,Wurst W,Harmelin A,Deussing JM,Eder M,Chen A

doi

10.1016/j.cmet.2016.04.017

subject

Has Abstract

pub_date

2016-06-14 00:00:00

pages

1185-1199

issue

6

eissn

1550-4131

issn

1932-7420

pii

S1550-4131(16)30169-3

journal_volume

23

pub_type

杂志文章

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