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Early Postnatal Caloric Restriction Protects Adult Male Intrauterine Growth–Restricted Offspring From Obesity

Postnatal ad libitum caloric intake superimposed on intrauterine growth restriction (IUGR) is associated with adult-onset obesity, insulin resistance, and type 2 diabetes mellitus (T2DM). We hypothesized that this paradigm of prenatal nutrient deprivation–induced programming can be reversed with the...

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Autores principales: Garg, Meena, Thamotharan, Manikkavasagar, Dai, Yun, Thamotharan, Shanthie, Shin, Bo-Chul, Stout, David, Devaskar, Sherin U.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3357266/
https://www.ncbi.nlm.nih.gov/pubmed/22461568
http://dx.doi.org/10.2337/db11-1347
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author Garg, Meena
Thamotharan, Manikkavasagar
Dai, Yun
Thamotharan, Shanthie
Shin, Bo-Chul
Stout, David
Devaskar, Sherin U.
author_facet Garg, Meena
Thamotharan, Manikkavasagar
Dai, Yun
Thamotharan, Shanthie
Shin, Bo-Chul
Stout, David
Devaskar, Sherin U.
author_sort Garg, Meena
collection PubMed
description Postnatal ad libitum caloric intake superimposed on intrauterine growth restriction (IUGR) is associated with adult-onset obesity, insulin resistance, and type 2 diabetes mellitus (T2DM). We hypothesized that this paradigm of prenatal nutrient deprivation–induced programming can be reversed with the introduction of early postnatal calorie restriction. Ten-month-old male rats exposed to either prenatal nutrient restriction with ad libitum postnatal intake (IUGR), pre- and postnatal nutrient restriction (IPGR), or postnatal nutrient restriction limited to the suckling phase (50% from postnatal [PN]1 to PN21) (PNGR) were compared with age-matched controls (CON). Visceral adiposity, metabolic profile, and insulin sensitivity by hyperinsulinemic-euglycemic clamps were examined. The 10-month-old male IUGR group had a 1.5- to 2.0-fold increase in subcutaneous and visceral fat (P < 0.0002) while remaining euglycemic, insulin sensitive, inactive, and exhibiting metabolic inflexibility (Vo(2)) versus CON. The IPGR group remained lean, euglycemic, insulin sensitive, and active while maintaining metabolic flexibility. The PNGR group was insulin sensitive, similar to IPGR, but less active while maintaining metabolic flexibility. We conclude that IUGR resulted in obesity without insulin resistance and energy metabolic perturbations prior to development of glucose intolerance and T2DM. Postnatal nutrient restriction superimposed on IUGR was protective, restoring metabolic normalcy to a lean and active phenotype.
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spelling pubmed-33572662013-06-01 Early Postnatal Caloric Restriction Protects Adult Male Intrauterine Growth–Restricted Offspring From Obesity Garg, Meena Thamotharan, Manikkavasagar Dai, Yun Thamotharan, Shanthie Shin, Bo-Chul Stout, David Devaskar, Sherin U. Diabetes Metabolism Postnatal ad libitum caloric intake superimposed on intrauterine growth restriction (IUGR) is associated with adult-onset obesity, insulin resistance, and type 2 diabetes mellitus (T2DM). We hypothesized that this paradigm of prenatal nutrient deprivation–induced programming can be reversed with the introduction of early postnatal calorie restriction. Ten-month-old male rats exposed to either prenatal nutrient restriction with ad libitum postnatal intake (IUGR), pre- and postnatal nutrient restriction (IPGR), or postnatal nutrient restriction limited to the suckling phase (50% from postnatal [PN]1 to PN21) (PNGR) were compared with age-matched controls (CON). Visceral adiposity, metabolic profile, and insulin sensitivity by hyperinsulinemic-euglycemic clamps were examined. The 10-month-old male IUGR group had a 1.5- to 2.0-fold increase in subcutaneous and visceral fat (P < 0.0002) while remaining euglycemic, insulin sensitive, inactive, and exhibiting metabolic inflexibility (Vo(2)) versus CON. The IPGR group remained lean, euglycemic, insulin sensitive, and active while maintaining metabolic flexibility. The PNGR group was insulin sensitive, similar to IPGR, but less active while maintaining metabolic flexibility. We conclude that IUGR resulted in obesity without insulin resistance and energy metabolic perturbations prior to development of glucose intolerance and T2DM. Postnatal nutrient restriction superimposed on IUGR was protective, restoring metabolic normalcy to a lean and active phenotype. American Diabetes Association 2012-06 2012-05-14 /pmc/articles/PMC3357266/ /pubmed/22461568 http://dx.doi.org/10.2337/db11-1347 Text en © 2012 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 Metabolism
Garg, Meena
Thamotharan, Manikkavasagar
Dai, Yun
Thamotharan, Shanthie
Shin, Bo-Chul
Stout, David
Devaskar, Sherin U.
Early Postnatal Caloric Restriction Protects Adult Male Intrauterine Growth–Restricted Offspring From Obesity
title Early Postnatal Caloric Restriction Protects Adult Male Intrauterine Growth–Restricted Offspring From Obesity
title_full Early Postnatal Caloric Restriction Protects Adult Male Intrauterine Growth–Restricted Offspring From Obesity
title_fullStr Early Postnatal Caloric Restriction Protects Adult Male Intrauterine Growth–Restricted Offspring From Obesity
title_full_unstemmed Early Postnatal Caloric Restriction Protects Adult Male Intrauterine Growth–Restricted Offspring From Obesity
title_short Early Postnatal Caloric Restriction Protects Adult Male Intrauterine Growth–Restricted Offspring From Obesity
title_sort early postnatal caloric restriction protects adult male intrauterine growth–restricted offspring from obesity
topic Metabolism
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3357266/
https://www.ncbi.nlm.nih.gov/pubmed/22461568
http://dx.doi.org/10.2337/db11-1347
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