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Two preoptic populations respond differently as temperature changes feeding

Nature communications · 2022-07-22

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Nature communications · Research frontiers

Two preoptic populations respond differently as temperature changes feeding

Two glutamatergic preoptic populations in mice connect to feeding-promoting and feeding-suppressing routes. Distinct calcium responses and interventions in downstream recipients reveal how ambient temperature relates to intake.

AI concept illustration: a mouse approaching food, cool and warm ambient light and two abstract neuronal groups; not an experimental image or an actual circuit map

Why do cold environments promote eating while heat reduces appetite? A study published in Nature Communications on July 22, 2022 identifies neighboring populations in the anteroventral and periventricular medial preoptic area, apMPOA, in mice. Both are glutamatergic but project to different targets: arcuate nucleus, ARC, and paraventricular hypothalamic nucleus, PVH. Environmental exposure, cellular calcium responses and feeding outcomes link ambient temperature with energy intake.

KEY FINDING

Activating apMPOA terminals in ARC promotes intake, while activation in PVH suppresses it. Inhibiting or reducing apMPOA-recipient PVH cells increases intake and diminishes measured temperature-dependent feeding differences.

Contents · 7 sections

Ambient temperature joins hunger as an influence

In the tested environments, heat reduces intake and cold increases it without corresponding rectal-temperature changes. Feeding adjustments may contribute to thermal balance rather than simply follow an already disrupted body temperature.

Fasting increases activity labeling in apMPOA, which declines after refeeding and overlaps substantially with glutamatergic cells. Population calcium likewise falls after feeding begins, without a corresponding GAD2-population change. The region links dietary state with thermoregulation.

Original figure 1Ambient temperature joins hunger as an influence
Ambient temperature joins hunger as an influence
Original Figure 1: temperature-related feeding, dietary-state activity labeling and population calcium; glutamatergic signals decline after eating begins.
Source: Qian S et al. · Nature communications · CC BY
Original figure and English caption ↗

Broad activation changes feeding alongside heat regulation

Broad glutamatergic apMPOA activation markedly reduces intake, increases tail heat dissipation, reduces brown-fat thermogenesis and lowers temperature. Mice also build nests. Tested GAD2 activation does not produce corresponding intake or temperature changes.

The scene involves more than appetite: heat balance and behavioral allocation also change. To distinguish outputs more closely associated with feeding, the team follows downstream projections and separates the broader regional effect into routes.

Original figure 2Broad activation changes feeding alongside heat regulation
Broad activation changes feeding alongside heat regulation
Original Figure 2: broad glutamatergic activation reduces intake alongside heat-dissipation, thermogenesis and temperature changes.
Source: Qian S et al. · Nature communications · CC BY
Original figure and English caption ↗

Excitatory outputs influence feeding in opposite directions

Activating apMPOA terminals in ARC increases intake; activating terminals in PVH decreases it. Both effects occur in tested cold, hot and neutral environments without corresponding rectal-temperature changes or prominent nesting.

ARC and PVH both regulate feeding but contain diverse cells. Destination helps explain behavioral direction beyond glutamatergic identity alone. A DMH output also accompanies reduced eating but prominently evokes nesting, making a direct feeding interpretation less clear.

Original figure 3Excitatory outputs influence feeding in opposite directions
Excitatory outputs influence feeding in opposite directions
Original Figure 3: ARC-terminal activation increases intake and PVH-terminal activation decreases it; DMH outcomes accompany other thermoregulatory behavior.
Source: Qian S et al. · Nature communications · CC BY
Original figure and English caption ↗

PVH recipients influence temperature-related differences

The study next labels downstream apMPOA recipients. Reducing or inhibiting ARC recipients lowers intake, while corresponding PVH-recipient interventions increase it. Recipient-side results complement terminal activation while targeting the cells themselves.

After PVH-recipient intervention, intake differences among cold, neutral and hot environments become nonsignificant. ARC-recipient intervention lowers intake while temperature differences persist. Both routes affect intake, but PVH recipients more prominently connect intake with environmental variation.

Original figure 5PVH recipients influence temperature-related differences
PVH recipients influence temperature-related differences
Original Figure 5: recipient-cell inhibition produces opposing intake effects; temperature comparisons within the inhibited PVH-recipient condition are nonsignificant.
Source: Qian S et al. · Nature communications · CC BY
Original figure and English caption ↗

Cold and warmth recruit different output populations

In ARC-projecting apMPOA cells, cold environments increase calcium without a corresponding heat response. PVH-projecting cells increase calcium in heat and decrease it in cold. Their different dynamics align with feeding-promoting and feeding-suppressing effects.

Local thermal-plate exposure differs: ARC-projecting cells show no significant response, while PVH-projecting cells mainly decline during local cooling. Whole-environment thermal challenges and local contact recruit the populations differently.

Original figure 6Cold and warmth recruit different output populations
Cold and warmth recruit different output populations
Original Figure 6: projection-defined calcium responses differ across ambient temperatures; local warmth is largely unresponsive, with a PVH-population decline during local cooling.
Source: Qian S et al. · Nature communications · CC BY
Original figure and English caption ↗

Neighboring cells receive different upstream inputs

Dual tracing identifies neighboring populations with limited overlap. Upstream anatomical tracing links PVH-projecting cells more strongly with dorsal lateral-parabrachial input and ARC-projecting cells with the external subregion, alongside other source differences.

Parabrachial regions are already implicated in thermal signaling; these findings refine the connectivity map. The new evidence describes input distributions, while their functional contribution to feeding awaits direct intervention.

PVH-projecting cells also receive more labeling from posterior bed nucleus, solitary tract nucleus and amygdala-related sources. The populations belong to a broader information network that could bring bodily state and environmental cues together in feeding regulation.

Original figure 7Neighboring cells receive different upstream inputs
Neighboring cells receive different upstream inputs
Original Figure 7: projection populations overlap sparsely and differ in anatomical input labeling from parabrachial and other regions.
Source: Qian S et al. · Nature communications · CC BY
Original figure and English caption ↗

Molecular profiles help distinguish the populations

Transcript comparisons and in-situ labeling show more GalR1 expression in ARC-projecting cells and more apelin receptor Aplnr in PVH-projecting cells. Neither exclusively labels every member. Local pharmacology alters intake, identifying candidates for further study.

Using adult female and male mice, the study links environment and dietary state with two output routes. It describes distinct neighboring responses and coordination rather than one uniform appetite switch. Specific recipient identities, upstream thermal inputs and receptor functions remain to be connected.

Drug effects also depend on context. NPY promotes intake at neutral temperature but has no significant effect in hot or cold conditions; tested NPY1-receptor blockade also changes intake nonsignificantly. Molecular effects remain dependent on the particular setting.

Original figure 8Molecular profiles help distinguish the populations
Molecular profiles help distinguish the populations
Original Figure 8: projection-associated transcripts, local pharmacology and receptor colabeling provide partial molecular distinctions between populations.
Source: Qian S et al. · Nature communications · CC BY
Original figure and English caption ↗

Publication details

Qian S, Yan S, Pang R, Zhang J, Liu K, Shi Z, Wang Z, Chen P, Zhang Y, Luo T, Hu X, Xiong Y, Zhou Y.
A temperature-regulated circuit for feeding behavior
Nature communications · 2022-07-22
DOI: 10.1038/s41467-022-31917-w