Defined Paraventricular Hypothalamic Populations Exhibit Differential Responses to Food Contingent on Caloric State

Chia Li; Jovana Navarrete; Jing Liang-Guallpa; Chunxia Lu; Samuel C Funderburk; Rui B Chang; Stephen D Liberles; David P Olson; Michael J Krashes

doi:10.1016/j.cmet.2018.10.016

Defined Paraventricular Hypothalamic Populations Exhibit Differential Responses to Food Contingent on Caloric State

Cell Metab. 2019 Mar 5;29(3):681-694.e5. doi: 10.1016/j.cmet.2018.10.016. Epub 2018 Nov 21.

Authors

Chia Li¹, Jovana Navarrete¹, Jing Liang-Guallpa², Chunxia Lu³, Samuel C Funderburk¹, Rui B Chang⁴, Stephen D Liberles⁴, David P Olson³, Michael J Krashes⁵

Affiliations

¹ Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, MD 20892, USA; National Institute on Drug Abuse (NIDA), National Institutes of Health, Baltimore, MD 21224, USA.
² Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, MD 20892, USA; Brown University Graduate Partnerships Program, Providence, RI 02912, USA; National Institute on Drug Abuse (NIDA), National Institutes of Health, Baltimore, MD 21224, USA.
³ Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109, USA.
⁴ Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
⁵ Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, MD 20892, USA; National Institute on Drug Abuse (NIDA), National Institutes of Health, Baltimore, MD 21224, USA. Electronic address: michael.krashes@nih.gov.

Abstract

Understanding the neural framework behind appetite control is fundamental to developing effective therapies to combat the obesity epidemic. The paraventricular hypothalamus (PVH) is critical for appetite regulation, yet, the real-time, physiological response properties of PVH neurons to nutrients are unknown. Using a combination of fiber photometry, electrophysiology, immunohistochemistry, and neural manipulation strategies, we determined the population dynamics of four molecularly delineated PVH subsets implicated in feeding behavior: glucagon-like peptide 1 receptor (PVH^Glp1r), melanocortin-4 receptor (PVH^Mc4r), oxytocin (PVH^Oxt), and corticotropin-releasing hormone (PVH^Crh). We identified both calorie- and state-dependent sustained activity increases and decreases in PVH^Glp1r and PVH^Crh populations, respectively, while observing transient bulk changes of PVH^Mc4r, but no response in PVH^Oxt, neurons to food. Furthermore, we highlight the role of PVH^Glp1r neurons in orchestrating acute feeding behavior, independent of the anti-obesity drug liraglutide, and demonstrate the indispensability of PVH^Glp1r and PVH^Mc4r, but not PVH^{Oxt or} PVH^Crh neurons, in body weight maintenance.

Keywords: fast versus refed; feeding behavior; hypothalamus; obesity; photometry recordings; population dynamics.

Publication types

Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural

MeSH terms

Animals
Appetite Regulation / physiology*
Corticotropin-Releasing Hormone / metabolism*
Energy Intake / physiology
Energy Metabolism
Female
Glucagon-Like Peptide-1 Receptor / metabolism*
Male
Mice
Neurons / metabolism
Oxytocin / metabolism*
Paraventricular Hypothalamic Nucleus / metabolism*
Receptor, Melanocortin, Type 4 / metabolism*

Substances

Glp1r protein, mouse
Glucagon-Like Peptide-1 Receptor
Receptor, Melanocortin, Type 4
Oxytocin
Corticotropin-Releasing Hormone

Abstract

Publication types

MeSH terms

Substances

Grants and funding