Adipose PTEN acts as a downstream mediator of a brain-fat axis in environmental enrichment
Background/Objectives: Environmental enrichment (EE) is a physiological model to investigate brain-fat interactions. We previously discovered that EE activates the hypothalamic-sympathoneural adipocyte (HSA) axis via induction of brain-derived neurotrophic factor (BDNF), thus leading to sympathetic...
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Format: | Article |
Language: | English |
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Elsevier
2020-11-01
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Series: | Comprehensive Psychoneuroendocrinology |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2666497620300138 |
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doaj-db193b20920742c0a4544c1dda39dd34 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Wei Huang Nicholas J. Queen Travis B. McMurphy Seemaab Ali Ryan K. Wilkins Bhavya Appana Lei Cao |
spellingShingle |
Wei Huang Nicholas J. Queen Travis B. McMurphy Seemaab Ali Ryan K. Wilkins Bhavya Appana Lei Cao Adipose PTEN acts as a downstream mediator of a brain-fat axis in environmental enrichment Comprehensive Psychoneuroendocrinology Environmental enrichment PTEN Adipose tissue Sympathetic nervous system Lipolysis AAV |
author_facet |
Wei Huang Nicholas J. Queen Travis B. McMurphy Seemaab Ali Ryan K. Wilkins Bhavya Appana Lei Cao |
author_sort |
Wei Huang |
title |
Adipose PTEN acts as a downstream mediator of a brain-fat axis in environmental enrichment |
title_short |
Adipose PTEN acts as a downstream mediator of a brain-fat axis in environmental enrichment |
title_full |
Adipose PTEN acts as a downstream mediator of a brain-fat axis in environmental enrichment |
title_fullStr |
Adipose PTEN acts as a downstream mediator of a brain-fat axis in environmental enrichment |
title_full_unstemmed |
Adipose PTEN acts as a downstream mediator of a brain-fat axis in environmental enrichment |
title_sort |
adipose pten acts as a downstream mediator of a brain-fat axis in environmental enrichment |
publisher |
Elsevier |
series |
Comprehensive Psychoneuroendocrinology |
issn |
2666-4976 |
publishDate |
2020-11-01 |
description |
Background/Objectives: Environmental enrichment (EE) is a physiological model to investigate brain-fat interactions. We previously discovered that EE activates the hypothalamic-sympathoneural adipocyte (HSA) axis via induction of brain-derived neurotrophic factor (BDNF), thus leading to sympathetic stimulation of white adipose tissue (WAT) and an anti-obesity phenotype. Here, we investigate whether PTEN acts as a downstream mediator of the HSA axis in the EE. Methods: Mice were housed in EE for 4- and 16-week periods to determine how EE regulates adipose PTEN. Hypothalamic injections of adeno-associated viral (AAV) vectors expressing BDNF and a dominant negative form of its receptor were performed to assess the role of the HSA axis in adipose PTEN upregulation. A β-blocker, propranolol, and a denervation agent, 6-hydroydopamine, were administered to assess sympathetic signaling in the observed EE-PTEN phenotype. To determine whether inducing PTEN is sufficient to reproduce certain EE adipose remodeling, we overexpressed PTEN in WAT using an AAV vector. To determine whether adipose PTEN is necessary for the EE-mediated reduction in adipocyte size, we injected a rAAV vector expressing Cre recombinase to the WAT of adult PTENflox mice and placed the mice in EE. Results: EE upregulated adipose PTEN expression, which was associated with suppression of AKT and ERK phosphorylation, increased hormone-sensitive lipase (HSL) phosphorylation, and reduced adiposity. PTEN regulation was found to be controlled by the HSA axis—with the hypothalamic BDNF acting as the upstream mediator—and dependent on sympathetic innervation. AAV-mediated adipose PTEN overexpression recapitulated EE-mediated adipose changes including suppression of AKT and ERK phosphorylation, increased HSL phosphorylation, and reduced adipose mass, whereas PTEN knockdown blocked the EE-induced reduction of adipocyte size. Conclusions: These data suggest that adipose PTEN responds to environmental stimuli and serves as downstream mediator of WAT remodeling in the EE paradigm, resulting in decreased adipose mass and decreased adipocyte size. |
topic |
Environmental enrichment PTEN Adipose tissue Sympathetic nervous system Lipolysis AAV |
url |
http://www.sciencedirect.com/science/article/pii/S2666497620300138 |
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doaj-db193b20920742c0a4544c1dda39dd342021-05-04T07:33:28ZengElsevierComprehensive Psychoneuroendocrinology2666-49762020-11-014100013Adipose PTEN acts as a downstream mediator of a brain-fat axis in environmental enrichmentWei Huang0Nicholas J. Queen1Travis B. McMurphy2Seemaab Ali3Ryan K. Wilkins4Bhavya Appana5Lei Cao6Department of Cancer Biology & Genetics, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA; The Ohio State University Comprehensive Cancer Center, Columbus, OH, 43210, USADepartment of Cancer Biology & Genetics, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA; The Ohio State University Comprehensive Cancer Center, Columbus, OH, 43210, USADepartment of Cancer Biology & Genetics, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA; The Ohio State University Comprehensive Cancer Center, Columbus, OH, 43210, USADepartment of Cancer Biology & Genetics, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA; The Ohio State University Comprehensive Cancer Center, Columbus, OH, 43210, USADepartment of Cancer Biology & Genetics, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA; The Ohio State University Comprehensive Cancer Center, Columbus, OH, 43210, USADepartment of Cancer Biology & Genetics, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA; The Ohio State University Comprehensive Cancer Center, Columbus, OH, 43210, USADepartment of Cancer Biology & Genetics, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA; The Ohio State University Comprehensive Cancer Center, Columbus, OH, 43210, USA; Corresponding author. Department of Cancer Biology and Genetics College of Medicine The Ohio State University Columbus, OH, 43210, USA.Background/Objectives: Environmental enrichment (EE) is a physiological model to investigate brain-fat interactions. We previously discovered that EE activates the hypothalamic-sympathoneural adipocyte (HSA) axis via induction of brain-derived neurotrophic factor (BDNF), thus leading to sympathetic stimulation of white adipose tissue (WAT) and an anti-obesity phenotype. Here, we investigate whether PTEN acts as a downstream mediator of the HSA axis in the EE. Methods: Mice were housed in EE for 4- and 16-week periods to determine how EE regulates adipose PTEN. Hypothalamic injections of adeno-associated viral (AAV) vectors expressing BDNF and a dominant negative form of its receptor were performed to assess the role of the HSA axis in adipose PTEN upregulation. A β-blocker, propranolol, and a denervation agent, 6-hydroydopamine, were administered to assess sympathetic signaling in the observed EE-PTEN phenotype. To determine whether inducing PTEN is sufficient to reproduce certain EE adipose remodeling, we overexpressed PTEN in WAT using an AAV vector. To determine whether adipose PTEN is necessary for the EE-mediated reduction in adipocyte size, we injected a rAAV vector expressing Cre recombinase to the WAT of adult PTENflox mice and placed the mice in EE. Results: EE upregulated adipose PTEN expression, which was associated with suppression of AKT and ERK phosphorylation, increased hormone-sensitive lipase (HSL) phosphorylation, and reduced adiposity. PTEN regulation was found to be controlled by the HSA axis—with the hypothalamic BDNF acting as the upstream mediator—and dependent on sympathetic innervation. AAV-mediated adipose PTEN overexpression recapitulated EE-mediated adipose changes including suppression of AKT and ERK phosphorylation, increased HSL phosphorylation, and reduced adipose mass, whereas PTEN knockdown blocked the EE-induced reduction of adipocyte size. Conclusions: These data suggest that adipose PTEN responds to environmental stimuli and serves as downstream mediator of WAT remodeling in the EE paradigm, resulting in decreased adipose mass and decreased adipocyte size.http://www.sciencedirect.com/science/article/pii/S2666497620300138Environmental enrichmentPTENAdipose tissueSympathetic nervous systemLipolysisAAV |