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Developmental Programming by Maternal Insulin Resistance: Hyperinsulinemia, Glucose Intolerance, and Dysregulated Lipid Metabolism in Male Offspring of Insulin-Resistant Mice

Maternal obesity and gestational diabetes mellitus (GDM) are associated with obesity and diabetes risk in offspring. We tested whether maternal insulin resistance, which frequently coexists with GDM and obesity, could independently contribute to dysregulation of offspring metabolism. Female mice hap...

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Autores principales: Isganaitis, Elvira, Woo, Melissa, Ma, Huijuan, Chen, Michael, Kong, Wen, Lytras, Aristides, Sales, Vicencia, DeCoste-Lopez, Jennifer, Lee, Kyung-Ju, Leatherwood, Cianna, Lee, Deborah, Fitzpatrick, Connor, Gall, Walter, Watkins, Steven, Patti, Mary-Elizabeth
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3900545/
https://www.ncbi.nlm.nih.gov/pubmed/24186867
http://dx.doi.org/10.2337/db13-0558
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author Isganaitis, Elvira
Woo, Melissa
Ma, Huijuan
Chen, Michael
Kong, Wen
Lytras, Aristides
Sales, Vicencia
DeCoste-Lopez, Jennifer
Lee, Kyung-Ju
Leatherwood, Cianna
Lee, Deborah
Fitzpatrick, Connor
Gall, Walter
Watkins, Steven
Patti, Mary-Elizabeth
author_facet Isganaitis, Elvira
Woo, Melissa
Ma, Huijuan
Chen, Michael
Kong, Wen
Lytras, Aristides
Sales, Vicencia
DeCoste-Lopez, Jennifer
Lee, Kyung-Ju
Leatherwood, Cianna
Lee, Deborah
Fitzpatrick, Connor
Gall, Walter
Watkins, Steven
Patti, Mary-Elizabeth
author_sort Isganaitis, Elvira
collection PubMed
description Maternal obesity and gestational diabetes mellitus (GDM) are associated with obesity and diabetes risk in offspring. We tested whether maternal insulin resistance, which frequently coexists with GDM and obesity, could independently contribute to dysregulation of offspring metabolism. Female mice haploinsufficient for insulin receptor substrate-1 (IRS1-het) are hyperinsulinemic and insulin resistant during pregnancy, despite normal plasma glucose and body weight, and thus serve as a model of isolated maternal insulin resistance. Wild-type (WT) offspring of IRS1-het dams insulin resistance-exposed [IR-exposed] were compared with WT offspring of WT dams. Despite no differences in adiposity, male IR-exposed pups were glucose intolerant (P = 0.04) and hyperinsulinemic (1.3-fold increase, P = 0.02) by 1 month of age and developed progressive fasting hyperglycemia. Moreover, male IR-exposed pups challenged with high-fat diet exhibited insulin resistance. Liver lipidomic analysis of 3-week-old IR-exposed males revealed increases in the 16:1n7 fraction of several lipid classes, suggesting increased Scd1 activity. By 6 months of age, IR-exposed males had increased lipid accumulation in liver as well as increased plasma refed fatty acids, consistent with disrupted lipid metabolism. Our results indicate that isolated maternal insulin resistance, even in the absence of hyperglycemia or obesity, can promote metabolic perturbations in male offspring.
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spelling pubmed-39005452015-02-01 Developmental Programming by Maternal Insulin Resistance: Hyperinsulinemia, Glucose Intolerance, and Dysregulated Lipid Metabolism in Male Offspring of Insulin-Resistant Mice Isganaitis, Elvira Woo, Melissa Ma, Huijuan Chen, Michael Kong, Wen Lytras, Aristides Sales, Vicencia DeCoste-Lopez, Jennifer Lee, Kyung-Ju Leatherwood, Cianna Lee, Deborah Fitzpatrick, Connor Gall, Walter Watkins, Steven Patti, Mary-Elizabeth Diabetes Pathophysiology Maternal obesity and gestational diabetes mellitus (GDM) are associated with obesity and diabetes risk in offspring. We tested whether maternal insulin resistance, which frequently coexists with GDM and obesity, could independently contribute to dysregulation of offspring metabolism. Female mice haploinsufficient for insulin receptor substrate-1 (IRS1-het) are hyperinsulinemic and insulin resistant during pregnancy, despite normal plasma glucose and body weight, and thus serve as a model of isolated maternal insulin resistance. Wild-type (WT) offspring of IRS1-het dams insulin resistance-exposed [IR-exposed] were compared with WT offspring of WT dams. Despite no differences in adiposity, male IR-exposed pups were glucose intolerant (P = 0.04) and hyperinsulinemic (1.3-fold increase, P = 0.02) by 1 month of age and developed progressive fasting hyperglycemia. Moreover, male IR-exposed pups challenged with high-fat diet exhibited insulin resistance. Liver lipidomic analysis of 3-week-old IR-exposed males revealed increases in the 16:1n7 fraction of several lipid classes, suggesting increased Scd1 activity. By 6 months of age, IR-exposed males had increased lipid accumulation in liver as well as increased plasma refed fatty acids, consistent with disrupted lipid metabolism. Our results indicate that isolated maternal insulin resistance, even in the absence of hyperglycemia or obesity, can promote metabolic perturbations in male offspring. American Diabetes Association 2014-02 2014-01-16 /pmc/articles/PMC3900545/ /pubmed/24186867 http://dx.doi.org/10.2337/db13-0558 Text en © 2014 by the American Diabetes Association. Readers 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. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Pathophysiology
Isganaitis, Elvira
Woo, Melissa
Ma, Huijuan
Chen, Michael
Kong, Wen
Lytras, Aristides
Sales, Vicencia
DeCoste-Lopez, Jennifer
Lee, Kyung-Ju
Leatherwood, Cianna
Lee, Deborah
Fitzpatrick, Connor
Gall, Walter
Watkins, Steven
Patti, Mary-Elizabeth
Developmental Programming by Maternal Insulin Resistance: Hyperinsulinemia, Glucose Intolerance, and Dysregulated Lipid Metabolism in Male Offspring of Insulin-Resistant Mice
title Developmental Programming by Maternal Insulin Resistance: Hyperinsulinemia, Glucose Intolerance, and Dysregulated Lipid Metabolism in Male Offspring of Insulin-Resistant Mice
title_full Developmental Programming by Maternal Insulin Resistance: Hyperinsulinemia, Glucose Intolerance, and Dysregulated Lipid Metabolism in Male Offspring of Insulin-Resistant Mice
title_fullStr Developmental Programming by Maternal Insulin Resistance: Hyperinsulinemia, Glucose Intolerance, and Dysregulated Lipid Metabolism in Male Offspring of Insulin-Resistant Mice
title_full_unstemmed Developmental Programming by Maternal Insulin Resistance: Hyperinsulinemia, Glucose Intolerance, and Dysregulated Lipid Metabolism in Male Offspring of Insulin-Resistant Mice
title_short Developmental Programming by Maternal Insulin Resistance: Hyperinsulinemia, Glucose Intolerance, and Dysregulated Lipid Metabolism in Male Offspring of Insulin-Resistant Mice
title_sort developmental programming by maternal insulin resistance: hyperinsulinemia, glucose intolerance, and dysregulated lipid metabolism in male offspring of insulin-resistant mice
topic Pathophysiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3900545/
https://www.ncbi.nlm.nih.gov/pubmed/24186867
http://dx.doi.org/10.2337/db13-0558
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