Glutamatergic Preoptic Area Neurons That Express Leptin Receptors Drive Temperature-Dependent Body Weight Homeostasis
| Autor: | Andrei V. Derbenev, Sangho Yu, Andrea Zsombok, Kavon Rezai-Zadeh, Yanyan Jiang, Christopher D. Morrison, Heike Münzberg, Hans-Rudolf Berthoud, Emily Qualls-Creekmore |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
endocrine system medicine.medical_specialty Biology Energy homeostasis Body Temperature Eating Mice 03 medical and health sciences Glutamatergic Adipose Tissue Brown Glutamates Internal medicine Brown adipose tissue medicine Biological neural network Animals Homeostasis Neurons Leptin receptor General Neuroscience Body Weight Temperature Articles Thermoregulation Preoptic Area Preoptic area 030104 developmental biology medicine.anatomical_structure Endocrinology nervous system Receptors Adrenergic beta-3 Receptors Leptin Energy Metabolism Neuroscience Thermogenesis Body Temperature Regulation |
| Zdroj: | The Journal of Neuroscience. 36:5034-5046 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.0213-16.2016 |
| Popis: | The preoptic area (POA) regulates body temperature, but is not considered a site for body weight control. A subpopulation of POA neurons express leptin receptors (LepRbPOAneurons) and modulate reproductive function. However, LepRbPOAneurons project to sympathetic premotor neurons that control brown adipose tissue (BAT) thermogenesis, suggesting an additional role in energy homeostasis and body weight regulation. We determined the role of LepRbPOAneurons in energy homeostasis usingcre-dependent viral vectors to selectively activate these neurons and analyzed functional outcomes in mice. We show that LepRbPOAneurons mediate homeostatic adaptations to ambient temperature changes, and their pharmacogenetic activation drives robust suppression of energy expenditure and food intake, which lowers body temperature and body weight. Surprisingly, our data show that hypothermia-inducing LepRbPOAneurons are glutamatergic, while GABAergic POA neurons, originally thought to mediate warm-induced inhibition of sympathetic premotor neurons, have no effect on energy expenditure. Our data suggest a new view into the neurochemical and functional properties of BAT-related POA circuits and highlight their additional role in modulating food intake and body weight.SIGNIFICANCE STATEMENTBrown adipose tissue (BAT)-induced thermogenesis is a promising therapeutic target to treat obesity and metabolic diseases. The preoptic area (POA) controls body temperature by modulating BAT activity, but its role in body weight homeostasis has not been addressed. LepRbPOAneurons are BAT-related neurons and we show that they are sufficient to inhibit energy expenditure. We further show that LepRbPOAneurons modulate food intake and body weight, which is mediated by temperature-dependent homeostatic responses. We further found that LepRbPOAneurons are stimulatory glutamatergic neurons, contrary to prevalent models, providing a new view on thermoregulatory neural circuits. In summary, our study significantly expands our current understanding of central circuits and mechanisms that modulate energy homeostasis. |
| Databáze: | OpenAIRE |
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