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Hepatic Glucose Intolerance Precedes Hepatic Steatosis in the Male Aromatase Knockout (ArKO) Mouse

Estrogens are known to play a role in modulating metabolic processes within the body. The Aromatase knockout (ArKO) mice have been shown to harbor factors of Metabolic syndrome with central adiposity, hyperinsulinemia and male-specific hepatic steatosis. To determine the effects of estrogen ablation...

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Autores principales: Van Sinderen, Michelle L., Steinberg, Gregory R., Jørgensen, Sebastian B., To, Sarah Q., Knower, Kevin C., Clyne, Colin D., Honeyman, Jane, Chow, Jenny D., Herridge, Kerrie A., Jones, Margaret E. E., Simpson, Evan R., Boon, Wah Chin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3919708/
https://www.ncbi.nlm.nih.gov/pubmed/24520329
http://dx.doi.org/10.1371/journal.pone.0087230
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author Van Sinderen, Michelle L.
Steinberg, Gregory R.
Jørgensen, Sebastian B.
To, Sarah Q.
Knower, Kevin C.
Clyne, Colin D.
Honeyman, Jane
Chow, Jenny D.
Herridge, Kerrie A.
Jones, Margaret E. E.
Simpson, Evan R.
Boon, Wah Chin
author_facet Van Sinderen, Michelle L.
Steinberg, Gregory R.
Jørgensen, Sebastian B.
To, Sarah Q.
Knower, Kevin C.
Clyne, Colin D.
Honeyman, Jane
Chow, Jenny D.
Herridge, Kerrie A.
Jones, Margaret E. E.
Simpson, Evan R.
Boon, Wah Chin
author_sort Van Sinderen, Michelle L.
collection PubMed
description Estrogens are known to play a role in modulating metabolic processes within the body. The Aromatase knockout (ArKO) mice have been shown to harbor factors of Metabolic syndrome with central adiposity, hyperinsulinemia and male-specific hepatic steatosis. To determine the effects of estrogen ablation and subsequent replacement in males on whole body glucose metabolism, three- and six-month-old male ArKO mice were subjected to whole body glucose, insulin and pyruvate tolerance tests and analyzed for ensuing metabolic changes in liver, adipose tissue, and skeletal muscle. Estrogen-deficient male ArKO mice showed increased gonadal adiposity which was significantly reduced upon 17β-estradiol (E2) treatment. Concurrently, elevated ArKO serum leptin levels were significantly reduced upon E2 treatment and lowered serum adiponectin levels were restored to wild type levels. Three-month-old male ArKO mice were hyperglycemic, and both glucose and pyruvate intolerant. These phenotypes continued through to 6 months of age, highlighting a loss of glycemic control. ArKO livers displayed changes in gluconeogenic enzyme expression, and in insulin signaling pathways upon E2 treatment. Liver triglycerides were increased in the ArKO males only after 6 months of age, which could be reversed by E2 treatment. No differences were observed in insulin-stimulated ex vivo muscle glucose uptake nor changes in ArKO adipose tissue and muscle insulin signaling pathways. Therefore, we conclude that male ArKO mice develop hepatic glucose intolerance by the age of 3 months which precedes the sex-specific development of hepatic steatosis. This can be reversed upon the administration of exogenous E2.
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spelling pubmed-39197082014-02-11 Hepatic Glucose Intolerance Precedes Hepatic Steatosis in the Male Aromatase Knockout (ArKO) Mouse Van Sinderen, Michelle L. Steinberg, Gregory R. Jørgensen, Sebastian B. To, Sarah Q. Knower, Kevin C. Clyne, Colin D. Honeyman, Jane Chow, Jenny D. Herridge, Kerrie A. Jones, Margaret E. E. Simpson, Evan R. Boon, Wah Chin PLoS One Research Article Estrogens are known to play a role in modulating metabolic processes within the body. The Aromatase knockout (ArKO) mice have been shown to harbor factors of Metabolic syndrome with central adiposity, hyperinsulinemia and male-specific hepatic steatosis. To determine the effects of estrogen ablation and subsequent replacement in males on whole body glucose metabolism, three- and six-month-old male ArKO mice were subjected to whole body glucose, insulin and pyruvate tolerance tests and analyzed for ensuing metabolic changes in liver, adipose tissue, and skeletal muscle. Estrogen-deficient male ArKO mice showed increased gonadal adiposity which was significantly reduced upon 17β-estradiol (E2) treatment. Concurrently, elevated ArKO serum leptin levels were significantly reduced upon E2 treatment and lowered serum adiponectin levels were restored to wild type levels. Three-month-old male ArKO mice were hyperglycemic, and both glucose and pyruvate intolerant. These phenotypes continued through to 6 months of age, highlighting a loss of glycemic control. ArKO livers displayed changes in gluconeogenic enzyme expression, and in insulin signaling pathways upon E2 treatment. Liver triglycerides were increased in the ArKO males only after 6 months of age, which could be reversed by E2 treatment. No differences were observed in insulin-stimulated ex vivo muscle glucose uptake nor changes in ArKO adipose tissue and muscle insulin signaling pathways. Therefore, we conclude that male ArKO mice develop hepatic glucose intolerance by the age of 3 months which precedes the sex-specific development of hepatic steatosis. This can be reversed upon the administration of exogenous E2. Public Library of Science 2014-02-10 /pmc/articles/PMC3919708/ /pubmed/24520329 http://dx.doi.org/10.1371/journal.pone.0087230 Text en © 2014 Van Sinderen et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Van Sinderen, Michelle L.
Steinberg, Gregory R.
Jørgensen, Sebastian B.
To, Sarah Q.
Knower, Kevin C.
Clyne, Colin D.
Honeyman, Jane
Chow, Jenny D.
Herridge, Kerrie A.
Jones, Margaret E. E.
Simpson, Evan R.
Boon, Wah Chin
Hepatic Glucose Intolerance Precedes Hepatic Steatosis in the Male Aromatase Knockout (ArKO) Mouse
title Hepatic Glucose Intolerance Precedes Hepatic Steatosis in the Male Aromatase Knockout (ArKO) Mouse
title_full Hepatic Glucose Intolerance Precedes Hepatic Steatosis in the Male Aromatase Knockout (ArKO) Mouse
title_fullStr Hepatic Glucose Intolerance Precedes Hepatic Steatosis in the Male Aromatase Knockout (ArKO) Mouse
title_full_unstemmed Hepatic Glucose Intolerance Precedes Hepatic Steatosis in the Male Aromatase Knockout (ArKO) Mouse
title_short Hepatic Glucose Intolerance Precedes Hepatic Steatosis in the Male Aromatase Knockout (ArKO) Mouse
title_sort hepatic glucose intolerance precedes hepatic steatosis in the male aromatase knockout (arko) mouse
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3919708/
https://www.ncbi.nlm.nih.gov/pubmed/24520329
http://dx.doi.org/10.1371/journal.pone.0087230
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