Cargando…

Lactational High Fat Diet in Mice Causes Insulin Resistance and NAFLD in Male Offspring Which Is Partially Rescued by Maternal Metformin Treatment

Maternal metabolic disease and diet during pregnancy and lactation have important implications for the programming of offspring metabolic disease. In addition, high-fat diets during pregnancy and lactation can predispose the offspring to non-alcoholic fatty liver disease (NAFLD), a rising health thr...

Descripción completa

Detalles Bibliográficos
Autores principales: Hafner, Hannah, Mulcahy, Molly C., Carlson, Zach, Hartley, Phillip, Sun, Haijing, Westerhoff, Maria, Qi, Nathan, Bridges, Dave, Gregg, Brigid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8714922/
https://www.ncbi.nlm.nih.gov/pubmed/34977118
http://dx.doi.org/10.3389/fnut.2021.759690
_version_ 1784624033067696128
author Hafner, Hannah
Mulcahy, Molly C.
Carlson, Zach
Hartley, Phillip
Sun, Haijing
Westerhoff, Maria
Qi, Nathan
Bridges, Dave
Gregg, Brigid
author_facet Hafner, Hannah
Mulcahy, Molly C.
Carlson, Zach
Hartley, Phillip
Sun, Haijing
Westerhoff, Maria
Qi, Nathan
Bridges, Dave
Gregg, Brigid
author_sort Hafner, Hannah
collection PubMed
description Maternal metabolic disease and diet during pregnancy and lactation have important implications for the programming of offspring metabolic disease. In addition, high-fat diets during pregnancy and lactation can predispose the offspring to non-alcoholic fatty liver disease (NAFLD), a rising health threat in the U.S. We developed a model of maternal high-fat feeding exclusively during the lactation period. We previously showed that offspring from dams, given lactational high-fat diet (HFD), are predisposed to obesity, glucose intolerance, and inflammation. In separate experiments, we also showed that lactational metformin treatment can decrease offspring metabolic risk. The purpose of these studies was to understand the programming implications of lactational HFD on offspring metabolic liver disease risk. Dams were fed a 60% lard-based HFD from the day of delivery through the 21-day lactation period. A subset of dams was also given metformin as a co-treatment. Starting at weaning, the offspring were fed normal fat diet until 3 months of age; at which point, a subset was challenged with an additional HFD stressor. Lactational HFD led male offspring to develop hepatic insulin resistance. The post-weaning HFD challenge led male offspring to progress to NAFLD with more severe outcomes in the lactational HFD-challenged offspring. Co-administration of metformin to lactating dams on HFD partially rescued the offspring liver metabolic defects in males. Lactational HFD or post-weaning HFD had no impact on female offspring who maintained a normal insulin sensitivity and liver phenotype. These findings indicate that HFD, during the lactation period, programs the adult offspring to NAFLD risk in a sexually dimorphic manner. In addition, early life intervention with metformin via maternal exposure may prevent some of the liver programming caused by maternal HFD.
format Online
Article
Text
id pubmed-8714922
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-87149222021-12-30 Lactational High Fat Diet in Mice Causes Insulin Resistance and NAFLD in Male Offspring Which Is Partially Rescued by Maternal Metformin Treatment Hafner, Hannah Mulcahy, Molly C. Carlson, Zach Hartley, Phillip Sun, Haijing Westerhoff, Maria Qi, Nathan Bridges, Dave Gregg, Brigid Front Nutr Nutrition Maternal metabolic disease and diet during pregnancy and lactation have important implications for the programming of offspring metabolic disease. In addition, high-fat diets during pregnancy and lactation can predispose the offspring to non-alcoholic fatty liver disease (NAFLD), a rising health threat in the U.S. We developed a model of maternal high-fat feeding exclusively during the lactation period. We previously showed that offspring from dams, given lactational high-fat diet (HFD), are predisposed to obesity, glucose intolerance, and inflammation. In separate experiments, we also showed that lactational metformin treatment can decrease offspring metabolic risk. The purpose of these studies was to understand the programming implications of lactational HFD on offspring metabolic liver disease risk. Dams were fed a 60% lard-based HFD from the day of delivery through the 21-day lactation period. A subset of dams was also given metformin as a co-treatment. Starting at weaning, the offspring were fed normal fat diet until 3 months of age; at which point, a subset was challenged with an additional HFD stressor. Lactational HFD led male offspring to develop hepatic insulin resistance. The post-weaning HFD challenge led male offspring to progress to NAFLD with more severe outcomes in the lactational HFD-challenged offspring. Co-administration of metformin to lactating dams on HFD partially rescued the offspring liver metabolic defects in males. Lactational HFD or post-weaning HFD had no impact on female offspring who maintained a normal insulin sensitivity and liver phenotype. These findings indicate that HFD, during the lactation period, programs the adult offspring to NAFLD risk in a sexually dimorphic manner. In addition, early life intervention with metformin via maternal exposure may prevent some of the liver programming caused by maternal HFD. Frontiers Media S.A. 2021-12-15 /pmc/articles/PMC8714922/ /pubmed/34977118 http://dx.doi.org/10.3389/fnut.2021.759690 Text en Copyright © 2021 Hafner, Mulcahy, Carlson, Hartley, Sun, Westerhoff, Qi, Bridges and Gregg. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Nutrition
Hafner, Hannah
Mulcahy, Molly C.
Carlson, Zach
Hartley, Phillip
Sun, Haijing
Westerhoff, Maria
Qi, Nathan
Bridges, Dave
Gregg, Brigid
Lactational High Fat Diet in Mice Causes Insulin Resistance and NAFLD in Male Offspring Which Is Partially Rescued by Maternal Metformin Treatment
title Lactational High Fat Diet in Mice Causes Insulin Resistance and NAFLD in Male Offspring Which Is Partially Rescued by Maternal Metformin Treatment
title_full Lactational High Fat Diet in Mice Causes Insulin Resistance and NAFLD in Male Offspring Which Is Partially Rescued by Maternal Metformin Treatment
title_fullStr Lactational High Fat Diet in Mice Causes Insulin Resistance and NAFLD in Male Offspring Which Is Partially Rescued by Maternal Metformin Treatment
title_full_unstemmed Lactational High Fat Diet in Mice Causes Insulin Resistance and NAFLD in Male Offspring Which Is Partially Rescued by Maternal Metformin Treatment
title_short Lactational High Fat Diet in Mice Causes Insulin Resistance and NAFLD in Male Offspring Which Is Partially Rescued by Maternal Metformin Treatment
title_sort lactational high fat diet in mice causes insulin resistance and nafld in male offspring which is partially rescued by maternal metformin treatment
topic Nutrition
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8714922/
https://www.ncbi.nlm.nih.gov/pubmed/34977118
http://dx.doi.org/10.3389/fnut.2021.759690
work_keys_str_mv AT hafnerhannah lactationalhighfatdietinmicecausesinsulinresistanceandnafldinmaleoffspringwhichispartiallyrescuedbymaternalmetformintreatment
AT mulcahymollyc lactationalhighfatdietinmicecausesinsulinresistanceandnafldinmaleoffspringwhichispartiallyrescuedbymaternalmetformintreatment
AT carlsonzach lactationalhighfatdietinmicecausesinsulinresistanceandnafldinmaleoffspringwhichispartiallyrescuedbymaternalmetformintreatment
AT hartleyphillip lactationalhighfatdietinmicecausesinsulinresistanceandnafldinmaleoffspringwhichispartiallyrescuedbymaternalmetformintreatment
AT sunhaijing lactationalhighfatdietinmicecausesinsulinresistanceandnafldinmaleoffspringwhichispartiallyrescuedbymaternalmetformintreatment
AT westerhoffmaria lactationalhighfatdietinmicecausesinsulinresistanceandnafldinmaleoffspringwhichispartiallyrescuedbymaternalmetformintreatment
AT qinathan lactationalhighfatdietinmicecausesinsulinresistanceandnafldinmaleoffspringwhichispartiallyrescuedbymaternalmetformintreatment
AT bridgesdave lactationalhighfatdietinmicecausesinsulinresistanceandnafldinmaleoffspringwhichispartiallyrescuedbymaternalmetformintreatment
AT greggbrigid lactationalhighfatdietinmicecausesinsulinresistanceandnafldinmaleoffspringwhichispartiallyrescuedbymaternalmetformintreatment