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Cited by 94Birth, Development, and HealthGestational Diabetes Research and ManagementDiet, Metabolism, and Disease

Maternal obesity characterized by gestational diabetes increases the susceptibility of rat offspring to hepatic steatosis via a disrupted liver metabolome

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Pereira, Troy J., Fonseca, Mario A., Campbell, Kristyn E., Moyce, Brittany L., Cole, Laura K., Hatch, Grant M., Doucette, Christine A., Klein, Julianne +2 more·2015·The Journal of Physiology
DOI 10.1113/jp270429PMC PMC4532536
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Abstract

Key points: Gestational diabetes mellitus is a common complication of pregnancy, but its effects on the offspring are poorly understood. We developed a rat model of diet‐induced gestational diabetes mellitus that recapitulates many of the clinical features of the disease, including excessive gestational weight gain, glucose intolerance, hyperinsulinaemia and mild hyperglycaemia. Compared to the offspring of lean dams, exposure to gestational diabetes mellitus during the prenatal period resulted in obesity, hepatic steatosis and insulin resistance in young rat offspring that consumed a postnatal diet that was low in fat. The combination of maternal gestational diabetes mellitus and the postnatal consumption of a high‐fat diet by the offspring caused a more severe metabolic phenotype. Metabolomic profiling of the liver tissues of the offspring of gestational diabetic dams revealed accumulation of lipotoxic lipids and reduced phosphatidylethanolamine levels compared to the offspring of lean dams. The results establish that gestational diabetes mellitus is a driver of hepatic steatosis and insulin resistance in the offspring. Maternal obesity is associated with a high risk for gestational diabetes mellitus (GDM), which is a common complication of pregnancy. The influence of maternal obesity and GDM on the metabolic health of the offspring is poorly understood. We hypothesize that GDM associated with maternal obesity will cause obesity, insulin resistance and hepatic steatosis in the offspring. Female Sprague‐Dawley rats were fed a high‐fat (45%) and sucrose (HFS) diet to cause maternal obesity and GDM. Lean control pregnant rats received low‐fat (LF; 10%) diets. To investigate the interaction between the prenatal environment and postnatal diets, rat offspring were assigned to LF or HFS diets for 12 weeks, and insulin sensitivity and hepatic steatosis were evaluated. Pregnant GDM dams exhibited excessive gestational weight gain, hyperinsulinaemia and hyperglycaemia. Offspring of GDM dams gained more weight than the offspring of lean dams due to excess adiposity. The offspring of GDM dams also developed hepatic steatosis and insulin resistance. The postnatal consumption of a LF diet did not protect offspring of GDM dams against these metabolic disorders. Analysis of the hepatic metabolome revealed increased diacylglycerol and reduced phosphatidylethanolamine in the offspring of GDM dams compared to offspring of lean dams. Consistent with altered lipid metabolism, the expression of CTP:phosphoethanolamine cytidylyltransferase, and peroxisomal proliferator activated receptor‐α mRNA was reduced in the livers of GDM offspring. GDM exposure programs gene expression and hepatic metabolite levels and drives the development of hepatic steatosis and insulin resistance in young adult rat offspring.

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  • Gestational diabetes mellitus exposure conditioned 3-month-old offspring to the development of obesity, hepatic steatosis, glucose intolerance and pancreatic islet dysfunction.

    “we demonstrated that GDM exposure conditioned 3-month-old offspring to the development of obesity, hepatic steatosis, glucose intolerance [102] and pancreatic islet dysfunction [103,104] (Figure 1).”

    From Recent Experimental Studies of Maternal Obesity, Diabetes during Pregnancy and the Developmental Origins of Cardiovascular Disease (2022) · cites this paper as [102]

    The Abstract reports that offspring of GDM dams developed excess adiposity and hepatic steatosis. The Methods and Results report impaired insulin tolerance and insulin resistance in the offspring, but impaired glucose tolerance is reported for the dams, not the offspring. Pancreatic islet dysfunction is attached to citations [103,104], not to this source’s citation [102]. (LLM, conf=0.87)

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  • Hepatic steatosis in gestational diabetes mellitus exposed offspring was associated with an altered liver metabolome characterized by diacylglycerol accumulation and reduced phosphatidylethanolamine lipid species.

    “Hepatic steatosis in the GDM exposed offspring was associated with an altered liver metabolome that was characterized by diacylglycerol accumulation and reduced phosphatidylethanolamine lipid species [102].”

    From Recent Experimental Studies of Maternal Obesity, Diabetes during Pregnancy and the Developmental Origins of Cardiovascular Disease (2022) · cites this paper as [102]

  • Feeding female Sprague-Dawley rats a high-fat-and-sucrose diet prior to mating and throughout pregnancy increased pre-pregnancy weight, and during pregnancy caused excessive gestational weight gain, hyperglycemia and hyperinsulinemia and glucose intolerance at mid-gestation characteristic of gestational diabetes mellitus.

    “Our group showed that compared to low-fat-fed control females, feeding female Sprague-Dawley rats a high-fat-and-sucrose diet prior to mating and throughout pregnancy increased pre-pregnancy weight, and then during pregnancy caused excessive gestational weight gain, hyperglycemia and hyperinsulinemia and glucose intolerance at mid-gestation that are characteristic of GDM [102].”

    From Recent Experimental Studies of Maternal Obesity, Diabetes during Pregnancy and the Developmental Origins of Cardiovascular Disease (2022) · cites this paper as [102]

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Authors
Pereira, T. J., Fonseca, M. A., Campbell, K. E., Moyce, B. L., Cole, L. K., Hatch, G. M., Doucette, C. A., Klein, J., Aliani, M., & Dolinsky, V. W.
Affiliations
  • Children's Hospital Research Institute of Manitoba (CA)
  • Department of Pharmacology & Therapeutics
  • Shared Health (CA)
  • University of Manitoba (CA)
Corresponding author
Dolinsky, Vernon W.
ORCID
Venue
The Journal of Physiology
Publisher
Wiley
Published
2015-06-12
Volume
593
Issue
14
Pages
3181-3197
ISSN
  • 0022-3751 (ISSN-L)
  • 1469-7793
DOI
10.1113/jp270429
PMC
PMC4532536
OpenAlex
W2145307269
Cited by
94
References
7
Citations by year
2026: 6 · 2025: 6 · 2024: 2 · 2023: 11 · 2022: 13 · 2021: 11 · 2020: 10 · 2019: 10 · 2018: 7 · 2017: 6 · 2016: 7 · 2015: 4
FWCI
7.99
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • The Journal of Physiology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Children's Hospital Foundation of Manitoba
  • Children's Hospital Research Institute of Manitoba (CHF/CHRIM)
  • Manitoba Medical Services Foundation (MMSF) (#812.10)
  • Canadian Institutes of Health Research (CIHR) (#136885)
Topics
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
  • Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
Keywords
gestational diabetes mellitus, maternal obesity, hepatic steatosis, insulin resistance, offspring metabolic programming, liver metabolome, diacylglycerol, phosphatidylethanolamine, high-fat diet, gestational weight gain, hyperinsulinemia
MeSH terms
Animals, Diglycerides, Fatty Liver, Female, Liver, Obesity, Phosphatidylethanolamines, Pregnancy, Prenatal Exposure Delayed Effects, Sucrose, Diabetes, Gestational, Rats, Sprague-Dawley, PPAR alpha, Lipid Metabolism, Rats, Metabolome, Diet, High-Fat

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