Lateral Hypothalamic Neurotensin Neurons Orchestrate Dual Weight Loss Behaviors via Distinct Mechanisms
The central mechanism by which neurotensin (Nts) potentiates weight loss has remained elusive. We leveraged chemogenetics to reveal that Nts-expressing neurons of the lateral hypothalamic area (LHA) promote weight loss in mice by increasing volitional activity and restraining food intake. Intriguing...
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doaj-5909b73fc5a141f3828127bbc27795ea2020-11-25T00:27:23ZengElsevierCell Reports2211-12472017-12-0121113116312810.1016/j.celrep.2017.11.068Lateral Hypothalamic Neurotensin Neurons Orchestrate Dual Weight Loss Behaviors via Distinct MechanismsHillary L. Woodworth0Bethany G. Beekly1Hannah M. Batchelor2Raluca Bugescu3Patricia Perez-Bonilla4Laura E. Schroeder5Gina M. Leinninger6Department of Physiology, Michigan State University, East Lansing, MI 48824, USADepartment of Physiology, Michigan State University, East Lansing, MI 48824, USADepartment of Physiology, Michigan State University, East Lansing, MI 48824, USADepartment of Physiology, Michigan State University, East Lansing, MI 48824, USADepartment of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, USADepartment of Physiology, Michigan State University, East Lansing, MI 48824, USADepartment of Physiology, Michigan State University, East Lansing, MI 48824, USAThe central mechanism by which neurotensin (Nts) potentiates weight loss has remained elusive. We leveraged chemogenetics to reveal that Nts-expressing neurons of the lateral hypothalamic area (LHA) promote weight loss in mice by increasing volitional activity and restraining food intake. Intriguingly, these dual weight loss behaviors are mediated by distinct signaling pathways: Nts action via NtsR1 is essential for the anorectic effect of the LHA Nts circuit, but not for regulation of locomotor or drinking behavior. Furthermore, although LHA Nts neurons cannot reduce intake of freely available obesogenic foods, they effectively restrain motivated feeding in hungry, weight-restricted animals. LHA Nts neurons are thus vital mediators of central Nts action, particularly in the face of negative energy balance. Enhanced action via LHA Nts neurons may, therefore, be useful to suppress the increased appetitive drive that occurs after lifestyle-mediated weight loss and, hence, to prevent weight regain.http://www.sciencedirect.com/science/article/pii/S2211124717317205neurotensinneurotensin receptorlateral hypothalamic areafeedinglocomotor activitydrinkingobesityenergy balance |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hillary L. Woodworth Bethany G. Beekly Hannah M. Batchelor Raluca Bugescu Patricia Perez-Bonilla Laura E. Schroeder Gina M. Leinninger |
spellingShingle |
Hillary L. Woodworth Bethany G. Beekly Hannah M. Batchelor Raluca Bugescu Patricia Perez-Bonilla Laura E. Schroeder Gina M. Leinninger Lateral Hypothalamic Neurotensin Neurons Orchestrate Dual Weight Loss Behaviors via Distinct Mechanisms Cell Reports neurotensin neurotensin receptor lateral hypothalamic area feeding locomotor activity drinking obesity energy balance |
author_facet |
Hillary L. Woodworth Bethany G. Beekly Hannah M. Batchelor Raluca Bugescu Patricia Perez-Bonilla Laura E. Schroeder Gina M. Leinninger |
author_sort |
Hillary L. Woodworth |
title |
Lateral Hypothalamic Neurotensin Neurons Orchestrate Dual Weight Loss Behaviors via Distinct Mechanisms |
title_short |
Lateral Hypothalamic Neurotensin Neurons Orchestrate Dual Weight Loss Behaviors via Distinct Mechanisms |
title_full |
Lateral Hypothalamic Neurotensin Neurons Orchestrate Dual Weight Loss Behaviors via Distinct Mechanisms |
title_fullStr |
Lateral Hypothalamic Neurotensin Neurons Orchestrate Dual Weight Loss Behaviors via Distinct Mechanisms |
title_full_unstemmed |
Lateral Hypothalamic Neurotensin Neurons Orchestrate Dual Weight Loss Behaviors via Distinct Mechanisms |
title_sort |
lateral hypothalamic neurotensin neurons orchestrate dual weight loss behaviors via distinct mechanisms |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2017-12-01 |
description |
The central mechanism by which neurotensin (Nts) potentiates weight loss has remained elusive. We leveraged chemogenetics to reveal that Nts-expressing neurons of the lateral hypothalamic area (LHA) promote weight loss in mice by increasing volitional activity and restraining food intake. Intriguingly, these dual weight loss behaviors are mediated by distinct signaling pathways: Nts action via NtsR1 is essential for the anorectic effect of the LHA Nts circuit, but not for regulation of locomotor or drinking behavior. Furthermore, although LHA Nts neurons cannot reduce intake of freely available obesogenic foods, they effectively restrain motivated feeding in hungry, weight-restricted animals. LHA Nts neurons are thus vital mediators of central Nts action, particularly in the face of negative energy balance. Enhanced action via LHA Nts neurons may, therefore, be useful to suppress the increased appetitive drive that occurs after lifestyle-mediated weight loss and, hence, to prevent weight regain. |
topic |
neurotensin neurotensin receptor lateral hypothalamic area feeding locomotor activity drinking obesity energy balance |
url |
http://www.sciencedirect.com/science/article/pii/S2211124717317205 |
work_keys_str_mv |
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