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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...

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Autores principales: Shin, Andrew C., Filatova, Nika, Lindtner, Claudia, Chi, Tiffany, Degann, Seta, Oberlin, Douglas, Buettner, Christoph
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2017
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.
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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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