Prolonged Activation of Brain CB2 Signaling Modulates Hypothalamic Microgliosis and Astrogliosis in High Fat Diet-Fed Mice

Low-grade inflammation of the hypothalamus is associated with the disturbance of energy balance. The endocannabinoid system has been implicated in the development and maintenance of obesity as well as in the control of immune responses. The type 2 cannabinoid receptor (CB2) signaling has been associ...

Full description

Bibliographic Details
Main Authors: Rodrigo Rorato, Nathalia L. Ferreira, Franciane P. Oliveira, Higor J. Fideles, Tays A. Camilo, Jose Antunes-Rodrigues, Andre S. Mecawi, Lucila L. K. Elias
Format: Article
Language:English
Published: MDPI AG 2022-05-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/10/5527
_version_ 1797499244744015872
author Rodrigo Rorato
Nathalia L. Ferreira
Franciane P. Oliveira
Higor J. Fideles
Tays A. Camilo
Jose Antunes-Rodrigues
Andre S. Mecawi
Lucila L. K. Elias
author_facet Rodrigo Rorato
Nathalia L. Ferreira
Franciane P. Oliveira
Higor J. Fideles
Tays A. Camilo
Jose Antunes-Rodrigues
Andre S. Mecawi
Lucila L. K. Elias
author_sort Rodrigo Rorato
collection DOAJ
description Low-grade inflammation of the hypothalamus is associated with the disturbance of energy balance. The endocannabinoid system has been implicated in the development and maintenance of obesity as well as in the control of immune responses. The type 2 cannabinoid receptor (CB2) signaling has been associated with anti-inflammatory effects. Therefore, in high fat diet (HFD)-induced obese mice, we modulated CB2 signaling and investigated its effects on energy homeostasis and hypothalamic microgliosis/astrogliosis. We observed no effect on caloric intake and body weight gain in control diet-fed animals that received prolonged icv infusion of the CB2 receptor agonist HU308. Interestingly, we observed a decrease in glucose tolerance in HFD-fed animals treated with HU308. Prolonged icv infusion of HU308 increases astrogliosis in the ventromedial nucleus (VMH) of obese animals and reduced HFD-induced microgliosis in the hypothalamic arcuate (ARC) but not in the paraventricular (PVN) or VMH nuclei. These data indicate that central CB2 signaling modulates glucose homeostasis and glial reactivity in obesogenic conditions, irrespective of changes in body weight.
first_indexed 2024-03-10T03:44:42Z
format Article
id doaj.art-a8a0c6e83762426daee3fef06a448bdf
institution Directory Open Access Journal
issn 1661-6596
1422-0067
language English
last_indexed 2024-03-10T03:44:42Z
publishDate 2022-05-01
publisher MDPI AG
record_format Article
series International Journal of Molecular Sciences
spelling doaj.art-a8a0c6e83762426daee3fef06a448bdf2023-11-23T11:24:10ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-05-012310552710.3390/ijms23105527Prolonged Activation of Brain CB2 Signaling Modulates Hypothalamic Microgliosis and Astrogliosis in High Fat Diet-Fed MiceRodrigo Rorato0Nathalia L. Ferreira1Franciane P. Oliveira2Higor J. Fideles3Tays A. Camilo4Jose Antunes-Rodrigues5Andre S. Mecawi6Lucila L. K. Elias7Laboratory of Stress Neuroendocrinology, Department of Biophysics, Paulista Medical School, Federal University of Sao Paulo, Sao Paulo 04023-062, BrazilLaboratory of Stress Neuroendocrinology, Department of Biophysics, Paulista Medical School, Federal University of Sao Paulo, Sao Paulo 04023-062, BrazilLaboratory of Stress Neuroendocrinology, Department of Biophysics, Paulista Medical School, Federal University of Sao Paulo, Sao Paulo 04023-062, BrazilLaboratory of Stress Neuroendocrinology, Department of Biophysics, Paulista Medical School, Federal University of Sao Paulo, Sao Paulo 04023-062, BrazilLaboratory of Molecular Neuroendocrinology, Department of Biophysics, Paulista Medical School, Federal University of Sao Paulo, Sao Paulo 04023-062, BrazilDepartment of Physiology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, BrazilLaboratory of Molecular Neuroendocrinology, Department of Biophysics, Paulista Medical School, Federal University of Sao Paulo, Sao Paulo 04023-062, BrazilDepartment of Physiology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, BrazilLow-grade inflammation of the hypothalamus is associated with the disturbance of energy balance. The endocannabinoid system has been implicated in the development and maintenance of obesity as well as in the control of immune responses. The type 2 cannabinoid receptor (CB2) signaling has been associated with anti-inflammatory effects. Therefore, in high fat diet (HFD)-induced obese mice, we modulated CB2 signaling and investigated its effects on energy homeostasis and hypothalamic microgliosis/astrogliosis. We observed no effect on caloric intake and body weight gain in control diet-fed animals that received prolonged icv infusion of the CB2 receptor agonist HU308. Interestingly, we observed a decrease in glucose tolerance in HFD-fed animals treated with HU308. Prolonged icv infusion of HU308 increases astrogliosis in the ventromedial nucleus (VMH) of obese animals and reduced HFD-induced microgliosis in the hypothalamic arcuate (ARC) but not in the paraventricular (PVN) or VMH nuclei. These data indicate that central CB2 signaling modulates glucose homeostasis and glial reactivity in obesogenic conditions, irrespective of changes in body weight.https://www.mdpi.com/1422-0067/23/10/5527obesityCB2 signalinghypothalamic gliosisglycaemia
spellingShingle Rodrigo Rorato
Nathalia L. Ferreira
Franciane P. Oliveira
Higor J. Fideles
Tays A. Camilo
Jose Antunes-Rodrigues
Andre S. Mecawi
Lucila L. K. Elias
Prolonged Activation of Brain CB2 Signaling Modulates Hypothalamic Microgliosis and Astrogliosis in High Fat Diet-Fed Mice
International Journal of Molecular Sciences
obesity
CB2 signaling
hypothalamic gliosis
glycaemia
title Prolonged Activation of Brain CB2 Signaling Modulates Hypothalamic Microgliosis and Astrogliosis in High Fat Diet-Fed Mice
title_full Prolonged Activation of Brain CB2 Signaling Modulates Hypothalamic Microgliosis and Astrogliosis in High Fat Diet-Fed Mice
title_fullStr Prolonged Activation of Brain CB2 Signaling Modulates Hypothalamic Microgliosis and Astrogliosis in High Fat Diet-Fed Mice
title_full_unstemmed Prolonged Activation of Brain CB2 Signaling Modulates Hypothalamic Microgliosis and Astrogliosis in High Fat Diet-Fed Mice
title_short Prolonged Activation of Brain CB2 Signaling Modulates Hypothalamic Microgliosis and Astrogliosis in High Fat Diet-Fed Mice
title_sort prolonged activation of brain cb2 signaling modulates hypothalamic microgliosis and astrogliosis in high fat diet fed mice
topic obesity
CB2 signaling
hypothalamic gliosis
glycaemia
url https://www.mdpi.com/1422-0067/23/10/5527
work_keys_str_mv AT rodrigororato prolongedactivationofbraincb2signalingmodulateshypothalamicmicrogliosisandastrogliosisinhighfatdietfedmice
AT nathalialferreira prolongedactivationofbraincb2signalingmodulateshypothalamicmicrogliosisandastrogliosisinhighfatdietfedmice
AT francianepoliveira prolongedactivationofbraincb2signalingmodulateshypothalamicmicrogliosisandastrogliosisinhighfatdietfedmice
AT higorjfideles prolongedactivationofbraincb2signalingmodulateshypothalamicmicrogliosisandastrogliosisinhighfatdietfedmice
AT taysacamilo prolongedactivationofbraincb2signalingmodulateshypothalamicmicrogliosisandastrogliosisinhighfatdietfedmice
AT joseantunesrodrigues prolongedactivationofbraincb2signalingmodulateshypothalamicmicrogliosisandastrogliosisinhighfatdietfedmice
AT andresmecawi prolongedactivationofbraincb2signalingmodulateshypothalamicmicrogliosisandastrogliosisinhighfatdietfedmice
AT lucilalkelias prolongedactivationofbraincb2signalingmodulateshypothalamicmicrogliosisandastrogliosisinhighfatdietfedmice