Hypothalamic AgRP neurons regulate the hyperphagia of lactation.

Autor:	Catalbas K; University of Illinois Urbana-Champaign, Department of Molecular and Integrative Physiology, USA; University of Illinois Urbana-Champaign Neuroscience Program, USA., Pattnaik T; University of Illinois Urbana-Champaign, Department of Molecular and Integrative Physiology, USA., Congdon S; University of Illinois Urbana-Champaign, Department of Molecular and Integrative Physiology, USA., Nelson C; University of Illinois Urbana-Champaign, Department of Molecular and Integrative Physiology, USA., Villano LC; University of Illinois Urbana-Champaign, Department of Molecular and Integrative Physiology, USA., Sweeney P; University of Illinois Urbana-Champaign, Department of Molecular and Integrative Physiology, USA; University of Illinois Urbana-Champaign Neuroscience Program, USA. Electronic address: sweenp@illinois.edu.
Jazyk:	angličtina
Zdroj:	Molecular metabolism [Mol Metab] 2024 Aug; Vol. 86, pp. 101975. Date of Electronic Publication: 2024 Jun 24.
DOI:	10.1016/j.molmet.2024.101975
Abstrakt:	Objective: The lactational period is associated with profound hyperphagia to accommodate the energy demands of nursing. These changes are important for the long-term metabolic health of the mother and children as altered feeding during lactation increases the risk of mothers and offspring developing metabolic disorders later in life. However, the specific behavioral mechanisms and neural circuitry mediating the hyperphagia of lactation are incompletely understood. Methods: Here, we utilized home cage feeding devices to characterize the dynamics of feeding behavior in lactating mice. A combination of pharmacological and behavioral assays were utilized to determine how lactation alters meal structure, circadian aspects of feeding, hedonic feeding, and sensitivity to hunger and satiety signals in lactating mice. Finally, we utilized chemogenetic, immunohistochemical, and in vivo imaging approaches to characterize the role of hypothalamic agouti-related peptide (AgRP) neurons in lactational-hyperphagia. Results: The lactational period is associated with increased meal size, altered circadian patterns of feeding, reduced sensitivity to gut-brain satiety signals, and enhanced sensitivity to negative energy balance. Hypothalamic AgRP neurons display increased sensitivity to negative energy balance and altered in vivo activity during the lactational state. Further, using in vivo imaging approaches we demonstrate that AgRP neurons are directly activated by lactation. Chemogenetic inhibition of AgRP neurons acutely reduces feeding in lactating mice, demonstrating an important role for these neurons in lactational-hyperphagia. Conclusions: Together, these results show that lactation collectively alters multiple components of feeding behavior and position AgRP neurons as an important cellular substrate mediating the hyperphagia of lactation. Competing Interests: Declaration of competing interest P.S. owns stock in Courage Therapeutics. All the other authors declare no competing financial interests. (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)
Databáze:	MEDLINE
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