Refeeding activates neurons in the dorsomedial hypothalamus to inhibit food intake and promote positive valence

Imoto, Daigo; Yamamoto, Izumi; Matsunaga, Hirokazu; Yonekura, Toya; Lee, Ming-Liang; Kato, Kanji; Yamasaki, Takahiro; Xu, Shu-Cheng; Ishimoto, Taiga; Yamagata, Shinji; Otsuguro, Ken-ichi; Horiuchi, Motohiro; Iijima, Norifumi; Kimura, Kazuhiro; Toda, Chitoku

doi:10.1016/j.molmet.2021.101366

Cited by 22 publications

(19 citation statements)

References 59 publications

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“…It is noteworthy that all ORs assessed in the adult brain in this study show expression in the habenula and the hypothalamus. The hypothalamus has long been implicated in controlling food intake 27,28 and recent studies have implicated the habenula in food-related behaviors [29][30][31] . One interesting possibility is that the odors during food intake is transported into the brain and plays a role in the modulation of brain areas associated with food-related behaviors.…”

Section: Discussionmentioning

confidence: 99%

Expression of olfactory receptor genes in non-olfactory tissues in the developing and adult zebrafish

Jundi

Coutanceau

Bullier

et al. 2023

Sci Rep

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Since the discovery of olfactory receptor (OR) genes, their expression in non-olfactory tissues have been reported in rodents and humans. For example, mouse OR23 (mOR23) is expressed in sperm and muscle cells and has been proposed to play a role in chemotaxis and muscle migration, respectively. In addition, mouse mesencephalic dopaminergic neurons express various ORs, which respond to corresponding ligands. As the OR genes comprise the largest multigene family of G protein-coupled receptors in vertebrates (over 400 genes in human and 1000 in rodents), it has been difficult to categorize the extent of their diverse expression in non-olfactory tissues making it challenging to ascertain their function. The zebrafish genome contains significantly fewer OR genes at around 140 genes, and their expression pattern can be easily analyzed by carrying out whole mount in situ hybridization (ISH) assay in larvae. In this study, we found that 31 out of 36 OR genes, including or104-2, or108-1, or111-1, or125-4, or128-1, or128-5, 133-4, or133-7, or137-3 are expressed in various tissues, including the trunk, pharynx, pancreas and brain in the larvae. In addition, some OR genes are expressed in distinct brain regions such as the hypothalamus and the habenula in a dynamic temporal pattern between larvae, juvenile and adult zebrafish. We further confirmed that OR genes are expressed in non-olfactory tissues by RT-PCR in larvae and adults. These results indicate tight regulation of OR gene expression in the brain in a spatial and temporal manner and that the expression of OR genes in non-olfactory tissues are conserved in vertebrates. This study provides a framework to start investigating the function of ORs in the zebrafish brain.

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Section: Discussionmentioning

confidence: 99%

Expression of olfactory receptor genes in non-olfactory tissues in the developing and adult zebrafish

Jundi

Coutanceau

Bullier

et al. 2023

Sci Rep

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“…5). DMH CCK were previously implicated in refeeding after fasting and their activation reduced feeding promotes positive valence measured by place preference 38 . Remarkably, these neurons constitute a segregated population from DMH LepR neurons, suggesting that multiple neuronal DMH neuronal populations participate in energy homeostasis control.…”

Section: Discussionmentioning

confidence: 99%

“…Previously, a population of DMH neurons containing Cck, but negative for LepR, was shown to be electively activated by refeeding following prolonged fasting with their stimulation inhibiting feeding 38 .…”

Section: Cck Neurons Mediate the Increased Energy Expenditure Caused ...mentioning

confidence: 99%

A sex-specific thermogenic neurocircuit induced by stressful olfactory inputs.

Jovanović

Morones

Pool

et al. 2022

Preprint

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When detecting danger signals, animals exhibit adaptive changes in physiology and behavior aimed at increasing survival. In small prey animals, such as rodents, olfactory information plays a fundamental role in the perception of their environment and predator avoidance. Exposure to predation has been associated with reduced fatness in male rodents, but whether similar responses exist in both sexes is poorly understood. Exactly how the nervous system regulates weight in the context of danger perception remains unknown. Here we identify a sex-specific response leading to increased energy expenditure and elevated corticosterone in female mice exposed to predator smell or global stimulation of mitral and tufted cells of the olfactory bulb (OB). This response is absent in male mice and is not attenuated by gonadectomy in females. A population of neurons in the dorsomedial hypothalamus (DMH), selectively activated by aversive olfactory signals also receives polysynaptic afferents from mitral and tufted cells of the main OB (MOB). Cell sorting of projection neurons in the DMH receiving olfactory inputs and single-nucleus RNA-sequencing identify cholecystokinin (Cck)-expressing neurons as putative recipients of olfactory inputs. Chemogenetic stimulation of DMHCCK neurons recapitulates the effects of aversive olfactory stimulation on female energy expenditure. Taken together, our results suggest the existence of a female heightened stress reaction recruiting DMHCCK neurons to promote high energy utilization.

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“…D. Dot plot of average expression level (dot color) and percent expression (dot size) of genes of interest within DMH clusters. These genes were either previously identified in DMH 45,51,52,57 or validated as DMH markers by the Allen Brain Atlas Mouse Brain in situ hybridization data J. Heatmap of select genes that were differentially expressed across feeding conditions in DMH LepR neurons.…”

Section: Sf Alters Circadian Entrainment Gene Expression In Dmh Lepr ...mentioning

confidence: 99%

“…DMH neuron types were selected based on previously reported markers 51 , as well as known highly expressed genes in the DMH including Lepr, Pdyn, Ppp1r17, Cck and Grp 45,57,95 . Markers were validated via the Allen Brain Atlas mouse in situ hybridization data.…”

Section: Identification Of Dmh and Scn Neuronsmentioning

confidence: 99%

A leptin-responsive hypothalamic circuit inputs to the circadian feeding network

Tang

Godschall

Brennan

et al. 2023

Preprint

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Salient cues, such as the rising sun or the availability of food, play a crucial role in entraining biological clocks, allowing for effective behavioral adaptation and ultimately, survival. While the light-dependent entrainment of the central circadian pacemaker (suprachiasmatic nucleus, SCN) is relatively well defined, the molecular and neural mechanisms underlying entrainment associated with food availability remains elusive. Using single nucleus RNA sequencing during scheduled feeding (SF), we identified a leptin receptor (LepR) expressing neuron population in the dorsomedial hypothalamus (DMH) that upregulates circadian entrainment genes and exhibits rhythmic calcium activity prior to an anticipated meal. We found that disrupting DMHLepR neuron activity had a profound impact on both molecular and behavioral food entrainment. Specifically, silencing DMHLepR neurons, mis-timed exogenous leptin administration, or mis-timed chemogenetic stimulation of these neurons all interfered with the development of food entrainment. In a state of energy abundance, repetitive activation of DMHLepR neurons led to the partitioning of a secondary bout of circadian locomotor activity that was in phase with the stimulation and dependent on an intact SCN. Lastly, we discovered that a subpopulation of DMHLepR neurons project to the SCN with the capacity to influence the phase of the circadian clock. This leptin regulated circuit serves as a point of integration between the metabolic and circadian systems, facilitating the anticipation of meal times.

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Refeeding activates neurons in the dorsomedial hypothalamus to inhibit food intake and promote positive valence

Cited by 22 publications

References 59 publications

Expression of olfactory receptor genes in non-olfactory tissues in the developing and adult zebrafish

Expression of olfactory receptor genes in non-olfactory tissues in the developing and adult zebrafish

A sex-specific thermogenic neurocircuit induced by stressful olfactory inputs.

A leptin-responsive hypothalamic circuit inputs to the circadian feeding network

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