Maternal Fructose Intake Causes Developmental Reprogramming of Hepatic Mitochondrial Catalytic Activity and Lipid Metabolism in Weanling and Young Adult Offspring
Excess dietary fructose is a major public health concern, yet little is known about its influence on offspring development and later-life disease when consumed in excess during pregnancy. To determine whether increased maternal fructose intake could have long-term consequences on offspring health, w...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/2/999 |
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| author | Erin Vanessa LaRae Smith Rebecca Maree Dyson Christina M. G. Vanderboor Ousseynou Sarr Jane Anderson Mary J. Berry Timothy R. H. Regnault Lifeng Peng Clint Gray |
| author_facet | Erin Vanessa LaRae Smith Rebecca Maree Dyson Christina M. G. Vanderboor Ousseynou Sarr Jane Anderson Mary J. Berry Timothy R. H. Regnault Lifeng Peng Clint Gray |
| author_sort | Erin Vanessa LaRae Smith |
| collection | DOAJ |
| description | Excess dietary fructose is a major public health concern, yet little is known about its influence on offspring development and later-life disease when consumed in excess during pregnancy. To determine whether increased maternal fructose intake could have long-term consequences on offspring health, we investigated the effects of 10% <i>w</i>/<i>v</i> fructose water intake during preconception and pregnancy in guinea pigs. Female Dunkin Hartley guinea pigs were fed a control diet (CD) or fructose diet (FD; providing 16% of total daily caloric intake) ad libitum 60 days prior to mating and throughout gestation. Dietary interventions ceased at day of delivery. Offspring were culled at day 21 (D21) (weaning) and at 4 months (4 M) (young adult). Fetal exposure to excess maternal fructose intake significantly increased male and female triglycerides at D21 and 4 M and circulating palmitoleic acid and total omega-7 through day 0 (D0) to 4 M. Proteomic and functional analysis of significantly differentially expressed proteins revealed that FD offspring (D21 and 4 M) had significantly increased mitochondrial metabolic activities of β-oxidation, electron transport chain (ETC) and oxidative phosphorylation and reactive oxygen species production compared to the CD offspring. Western blotting analysis of both FD offspring validated the increased protein abundances of mitochondrial ETC complex II and IV, SREBP-1c and FAS, whereas VDAC1 expression was higher at D21 but lower at 4 M. We provide evidence demonstrating offspring programmed hepatic mitochondrial metabolism and de novo lipogenesis following excess maternal fructose exposure. These underlying asymptomatic programmed pathways may lead to a predisposition to metabolic dysfunction later in life. |
| first_indexed | 2024-03-10T01:16:19Z |
| format | Article |
| id | doaj.art-a60d217b8c69402095af81837d5f0087 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T01:16:19Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a60d217b8c69402095af81837d5f00872023-11-23T14:07:59ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-01-0123299910.3390/ijms23020999Maternal Fructose Intake Causes Developmental Reprogramming of Hepatic Mitochondrial Catalytic Activity and Lipid Metabolism in Weanling and Young Adult OffspringErin Vanessa LaRae Smith0Rebecca Maree Dyson1Christina M. G. Vanderboor2Ousseynou Sarr3Jane Anderson4Mary J. Berry5Timothy R. H. Regnault6Lifeng Peng7Clint Gray8Department of Paediatrics and Child Health, University of Otago, Wellington 6021, New ZealandDepartment of Paediatrics and Child Health, University of Otago, Wellington 6021, New ZealandDepartment of Physiology and Pharmacology, Western University, London, ON N6A 3K7, CanadaDepartment of Physiology and Pharmacology, Western University, London, ON N6A 3K7, CanadaDepartment of Pathology & Molecular Medicine, University of Otago, Wellington 6021, New ZealandDepartment of Paediatrics and Child Health, University of Otago, Wellington 6021, New ZealandDepartment of Obstetrics and Gynaecology, Children’s Health Research Institute, Western University, London, ON N6A 3K7, CanadaCentre for Biodiscovery and School of Biological Sciences, Victoria University of Wellington, Wellington 6021, New ZealandDepartment of Paediatrics and Child Health, University of Otago, Wellington 6021, New ZealandExcess dietary fructose is a major public health concern, yet little is known about its influence on offspring development and later-life disease when consumed in excess during pregnancy. To determine whether increased maternal fructose intake could have long-term consequences on offspring health, we investigated the effects of 10% <i>w</i>/<i>v</i> fructose water intake during preconception and pregnancy in guinea pigs. Female Dunkin Hartley guinea pigs were fed a control diet (CD) or fructose diet (FD; providing 16% of total daily caloric intake) ad libitum 60 days prior to mating and throughout gestation. Dietary interventions ceased at day of delivery. Offspring were culled at day 21 (D21) (weaning) and at 4 months (4 M) (young adult). Fetal exposure to excess maternal fructose intake significantly increased male and female triglycerides at D21 and 4 M and circulating palmitoleic acid and total omega-7 through day 0 (D0) to 4 M. Proteomic and functional analysis of significantly differentially expressed proteins revealed that FD offspring (D21 and 4 M) had significantly increased mitochondrial metabolic activities of β-oxidation, electron transport chain (ETC) and oxidative phosphorylation and reactive oxygen species production compared to the CD offspring. Western blotting analysis of both FD offspring validated the increased protein abundances of mitochondrial ETC complex II and IV, SREBP-1c and FAS, whereas VDAC1 expression was higher at D21 but lower at 4 M. We provide evidence demonstrating offspring programmed hepatic mitochondrial metabolism and de novo lipogenesis following excess maternal fructose exposure. These underlying asymptomatic programmed pathways may lead to a predisposition to metabolic dysfunction later in life.https://www.mdpi.com/1422-0067/23/2/999maternal fructoseexcess fructose intakedevelopmental programminghepatic metabolismmitochondrial metabolismmitochondrial function |
| spellingShingle | Erin Vanessa LaRae Smith Rebecca Maree Dyson Christina M. G. Vanderboor Ousseynou Sarr Jane Anderson Mary J. Berry Timothy R. H. Regnault Lifeng Peng Clint Gray Maternal Fructose Intake Causes Developmental Reprogramming of Hepatic Mitochondrial Catalytic Activity and Lipid Metabolism in Weanling and Young Adult Offspring International Journal of Molecular Sciences maternal fructose excess fructose intake developmental programming hepatic metabolism mitochondrial metabolism mitochondrial function |
| title | Maternal Fructose Intake Causes Developmental Reprogramming of Hepatic Mitochondrial Catalytic Activity and Lipid Metabolism in Weanling and Young Adult Offspring |
| title_full | Maternal Fructose Intake Causes Developmental Reprogramming of Hepatic Mitochondrial Catalytic Activity and Lipid Metabolism in Weanling and Young Adult Offspring |
| title_fullStr | Maternal Fructose Intake Causes Developmental Reprogramming of Hepatic Mitochondrial Catalytic Activity and Lipid Metabolism in Weanling and Young Adult Offspring |
| title_full_unstemmed | Maternal Fructose Intake Causes Developmental Reprogramming of Hepatic Mitochondrial Catalytic Activity and Lipid Metabolism in Weanling and Young Adult Offspring |
| title_short | Maternal Fructose Intake Causes Developmental Reprogramming of Hepatic Mitochondrial Catalytic Activity and Lipid Metabolism in Weanling and Young Adult Offspring |
| title_sort | maternal fructose intake causes developmental reprogramming of hepatic mitochondrial catalytic activity and lipid metabolism in weanling and young adult offspring |
| topic | maternal fructose excess fructose intake developmental programming hepatic metabolism mitochondrial metabolism mitochondrial function |
| url | https://www.mdpi.com/1422-0067/23/2/999 |
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