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Insulin Receptor Signaling in POMC, but Not AgRP, Neurons Controls Adipose Tissue Insulin Action
Insulin is a key regulator of adipose tissue lipolysis, and impaired adipose tissue insulin action results in unrestrained lipolysis and lipotoxicity, which are hallmarks of the metabolic syndrome and diabetes. Insulin regulates adipose tissue metabolism through direct effects on adipocytes and thro...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440019/ https://www.ncbi.nlm.nih.gov/pubmed/28385803 http://dx.doi.org/10.2337/db16-1238 |
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author | Shin, Andrew C. Filatova, Nika Lindtner, Claudia Chi, Tiffany Degann, Seta Oberlin, Douglas Buettner, Christoph |
author_facet | Shin, Andrew C. Filatova, Nika Lindtner, Claudia Chi, Tiffany Degann, Seta Oberlin, Douglas Buettner, Christoph |
author_sort | Shin, Andrew C. |
collection | PubMed |
description | Insulin is a key regulator of adipose tissue lipolysis, and impaired adipose tissue insulin action results in unrestrained lipolysis and lipotoxicity, which are hallmarks of the metabolic syndrome and diabetes. Insulin regulates adipose tissue metabolism through direct effects on adipocytes and through signaling in the central nervous system by dampening sympathetic outflow to the adipose tissue. Here we examined the role of insulin signaling in agouti-related protein (AgRP) and pro-opiomelanocortin (POMC) neurons in regulating hepatic and adipose tissue insulin action. Mice lacking the insulin receptor in AgRP neurons (AgRP IR KO) exhibited impaired hepatic insulin action because the ability of insulin to suppress hepatic glucose production (hGP) was reduced, but the ability of insulin to suppress lipolysis was unaltered. To the contrary, in POMC IR KO mice, insulin lowered hGP but failed to suppress adipose tissue lipolysis. High-fat diet equally worsened glucose tolerance in AgRP and POMC IR KO mice and their respective controls but increased hepatic triglyceride levels only in POMC IR KO mice, consistent with impaired lipolytic regulation resulting in fatty liver. These data suggest that although insulin signaling in AgRP neurons is important in regulating glucose metabolism, insulin signaling in POMC neurons controls adipose tissue lipolysis and prevents high-fat diet–induced hepatic steatosis. |
format | Online Article Text |
id | pubmed-5440019 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-54400192018-06-01 Insulin Receptor Signaling in POMC, but Not AgRP, Neurons Controls Adipose Tissue Insulin Action Shin, Andrew C. Filatova, Nika Lindtner, Claudia Chi, Tiffany Degann, Seta Oberlin, Douglas Buettner, Christoph Diabetes Metabolism Insulin is a key regulator of adipose tissue lipolysis, and impaired adipose tissue insulin action results in unrestrained lipolysis and lipotoxicity, which are hallmarks of the metabolic syndrome and diabetes. Insulin regulates adipose tissue metabolism through direct effects on adipocytes and through signaling in the central nervous system by dampening sympathetic outflow to the adipose tissue. Here we examined the role of insulin signaling in agouti-related protein (AgRP) and pro-opiomelanocortin (POMC) neurons in regulating hepatic and adipose tissue insulin action. Mice lacking the insulin receptor in AgRP neurons (AgRP IR KO) exhibited impaired hepatic insulin action because the ability of insulin to suppress hepatic glucose production (hGP) was reduced, but the ability of insulin to suppress lipolysis was unaltered. To the contrary, in POMC IR KO mice, insulin lowered hGP but failed to suppress adipose tissue lipolysis. High-fat diet equally worsened glucose tolerance in AgRP and POMC IR KO mice and their respective controls but increased hepatic triglyceride levels only in POMC IR KO mice, consistent with impaired lipolytic regulation resulting in fatty liver. These data suggest that although insulin signaling in AgRP neurons is important in regulating glucose metabolism, insulin signaling in POMC neurons controls adipose tissue lipolysis and prevents high-fat diet–induced hepatic steatosis. American Diabetes Association 2017-06 2017-04-06 /pmc/articles/PMC5440019/ /pubmed/28385803 http://dx.doi.org/10.2337/db16-1238 Text en © 2017 by the American Diabetes Association. http://www.diabetesjournals.org/content/licenseReaders may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license. |
spellingShingle | Metabolism Shin, Andrew C. Filatova, Nika Lindtner, Claudia Chi, Tiffany Degann, Seta Oberlin, Douglas Buettner, Christoph Insulin Receptor Signaling in POMC, but Not AgRP, Neurons Controls Adipose Tissue Insulin Action |
title | Insulin Receptor Signaling in POMC, but Not AgRP, Neurons Controls Adipose Tissue Insulin Action |
title_full | Insulin Receptor Signaling in POMC, but Not AgRP, Neurons Controls Adipose Tissue Insulin Action |
title_fullStr | Insulin Receptor Signaling in POMC, but Not AgRP, Neurons Controls Adipose Tissue Insulin Action |
title_full_unstemmed | Insulin Receptor Signaling in POMC, but Not AgRP, Neurons Controls Adipose Tissue Insulin Action |
title_short | Insulin Receptor Signaling in POMC, but Not AgRP, Neurons Controls Adipose Tissue Insulin Action |
title_sort | insulin receptor signaling in pomc, but not agrp, neurons controls adipose tissue insulin action |
topic | Metabolism |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440019/ https://www.ncbi.nlm.nih.gov/pubmed/28385803 http://dx.doi.org/10.2337/db16-1238 |
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