Cholinergic neurons in the dorsomedial hypothalamus regulate mouse brown adipose tissue metabolism

• DOI: 10.1016/j.molmet.2015.03.006
• Publication Date: 2015-04-11T08:01:17Z
• Authors: Jae Hoon Jeong; Dong Kun Lee; Clemence Blouet; Henry H. Ruiz; Christoph Buettner; Streamson Chua; Gary J. Schwartz; Young-Hwan Jo
• Keywords: 0301 basic medicine; Serotonin; 03 medical and health sciences; Muscarinic; Hypothalamus; Original Article; Neuronal tracing; Nicotinic; Internal medicine; RC31-1245; Acetylcholine

Brown adipose tissue (BAT) thermogenesis is critical in maintaining body temperature. The dorsomedial hypothalamus (DMH) integrates cutaneous thermosensory signals and regulates adaptive thermogenesis. Here, we study the function synaptic connectivity of input from DMH cholinergic neurons to sympathetic premotor raphe pallidus (Rpa).In order selectively manipulate neuron activity, generated transgenic mice expressing channelrhodopsin fused yellow fluorescent protein (YFP) (choline acetyltransferase (ChAT)-Cre::ChR2-YFP) with Cre-LoxP technique. In addition, used an adeno-associated virus carrying Cre recombinase gene delete floxed Chat DMH. Physiological studies response optogenetic stimulation were combined expression immunocytochemical analyses.A subset are ChAT-immunopositive neurons. activity these elevated by warm ambient A phenotype-specific neuronal tracing shows that directly project serotonergic Rpa. Optical decreases BAT which associated reduced core Furthermore, uncoupling 1 (Ucp1) peroxisome proliferator-activated receptor γ coactivator α (Pgc1α) mRNAs, markers activity. Injection M2-selective muscarinic antagonists into 4th ventricle abolishes effect optical stimulation. Single cell qRT-PCR analysis retrogradely identified BAT-projecting Rpa all M2 receptor-expressing contain tryptophan hydroxylase 2. animals lacking DMH, exposure temperature reduces neither Ucp1 nor Pgc1α mRNA expression.DMH send efferent Elevated this area through activation mAChRs on Therefore, direct DMH(ACh)-Rpa(5-HT) pathway may mediate physiological heat-defense responses environmental