Hypothalamic control of interoceptive hunger

Study authors Justin Siemian and Sarah Sarsfield

Featured Paper of the Month – December 2021

Published in Current Biology by Justin Siemian, Sarah Sarsfield, Yeka Aponte of the NIDA IRP Neuronal Circuits and Behavior Unit.

Summary

Regulating food intake is essential for survival and many factors influence feeding behaviors beyond caloric need or “hunger”. Despite this, some neurons that drive feeding in mice are routinely referred to as ‘‘hunger neurons,’ whereas others are not. To understand how specific hypothalamic neurons control interoceptive hunger, we trained mice to discriminate feelings of “hunger” from satiety. We then used optogenetics to manipulate the activity of three hypothalamic neuronal populations with well-known effects on feeding while mice performed this behavioral task. We found that arcuate nucleus AGRP neurons drive a hunger-like internal state, whereas GABAergic and glutamatergic lateral hypothalamic neurons do not. Our study highlights the complexity of hypothalamic feeding regulation and can be used as a framework to characterize how other neuronal circuits affect hunger and identify potential therapeutic targets for eating disorders.

Publication Information

Siemian, Justin N; Arenivar, Miguel A; Sarsfield, Sarah; Aponte, Yeka

Hypothalamic control of interoceptive hunger Journal Article

In: Curr Biol, vol. 31, no. 17, pp. 3797–3809.e5, 2021, ISSN: 1879-0445.

Abstract | Links

@article{pmid34273280,

title = {Hypothalamic control of interoceptive hunger},

author = {Justin N Siemian and Miguel A Arenivar and Sarah Sarsfield and Yeka Aponte},

url = {https://pubmed.ncbi.nlm.nih.gov/34273280/},

doi = {10.1016/j.cub.2021.06.048},

issn = {1879-0445},

year  = {2021},

date = {2021-09-01},

urldate = {2021-09-01},

journal = {Curr Biol},

volume = {31},

number = {17},

pages = {3797--3809.e5},

abstract = {While energy balance is critical to survival, many factors influence food intake beyond caloric need or "hunger." Despite this, some neurons that drive feeding in mice are routinely referred to as "hunger neurons," whereas others are not. To understand how specific hypothalamic circuits control interoceptive hunger, we trained mice to discriminate fasted from sated periods. We then manipulated three hypothalamic neuronal populations with well-known effects on feeding while mice performed this task. While activation of ARC neurons in sated mice caused mice to report being food-restricted, LH neuron activation or LH neuron inhibition did not. In contrast, LH neuron inhibition or LH neuron activation in fasted mice attenuated natural hunger, whereas ARC neuron inhibition did not. Each neuronal population evoked distinct effects on food consumption and reward. After satiety- or sickness-induced devaluation, ARC neurons drove calorie-specific feeding, while LH neurons drove calorie-indiscriminate food intake. Our data support a role for ARC neurons in homeostatic feeding and implicate them in driving a hunger-like internal state that directs behavior toward caloric food sources. Moreover, manipulations of LH circuits did not evoke hunger-like effects in sated mice, suggesting that they may govern feeding more related to reward, compulsion, or generalized consumption than to energy balance, but also that these LH circuits can be powerful negative appetite modulators in fasted mice. This study highlights the complexity of hypothalamic feeding regulation and can be used as a framework to characterize how other neuronal circuits affect hunger and identify potential therapeutic targets for eating disorders.},

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pubstate = {published},

tppubtype = {article}

}