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Publication
Paraventricular, subparaventricular and periventricular hypothalamic
IRS4-expressing neurons are required for normal energy balance.
Authors Sutton AK, Gonzalez IE, Sadagurski M, Rajala M, Lu C, Allison MB, Adams JM,
Myers MG, White MF, Olson DP
Submitted By Submitted Externally on 1/10/2022
Status Published
Journal Scientific reports
Year 2020
Date Published 3/1/2020
Volume : Pages 10 : 5546
PubMed Reference 32218485
Abstract Understanding the neural components modulating feeding-related behavior and
energy expenditure is crucial to combating obesity and its comorbidities.
Neurons within the paraventricular nucleus of the hypothalamus (PVH) are a key
component of the satiety response; activation of the PVH decreases feeding and
increases energy expenditure, thereby promoting negative energy balance. In
contrast, PVH ablation or silencing in both rodents and humans leads to
substantial obesity. Recent studies have identified genetically-defined PVH
subpopulations that control discrete aspects of energy balance (e.g. oxytocin
(OXT), neuronal nitric oxide synthase 1 (NOS1), melanocortin 4-receptor (MC4R),
prodynorphin (PDYN)). We previously demonstrated that non-OXT NOS1PVH neurons
contribute to PVH-mediated feeding suppression. Here, we identify and
characterize a non-OXT, non-NOS1 subpopulation of PVH and peri-PVH neurons
expressing insulin-receptor substrate 4 (IRS4PVH) involved in energy balance
control. Using Cre-dependent viral tools to activate, trace and silence these
neurons, we highlight the sufficiency and necessity of IRS4PVH neurons in normal
feeding and energy expenditure regulation. Furthermore, we demonstrate that
IRS4PVH neurons lie within a complex hypothalamic circuitry that engages
distinct hindbrain regions and is innervated by discrete upstream hypothalamic
sites. Overall, we reveal a requisite role for IRS4PVH neurons in PVH-mediated
energy balance which raises the possibility of developing novel approaches
targeting IRS4PVH neurons for anti-obesity therapies.




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