Maternal obesity characterized by gestational diabetes increases the susceptibility of rat offspring to hepatic steatosis via a disrupted liver metabolome.
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.
Department of Pharmacology & Therapeutics.|Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Research Theme.|Children's Hospital Research Institute of Manitoba.
Troy J
TJ
Pereira
Department of Pharmacology & Therapeutics.|Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Research Theme.|Children's Hospital Research Institute of Manitoba.
Mario A
MA
Fonseca
Department of Pharmacology & Therapeutics.|Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Research Theme.|Children's Hospital Research Institute of Manitoba.
Kristyn E
KE
Campbell
Department of Pharmacology & Therapeutics.|Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Research Theme.|Children's Hospital Research Institute of Manitoba.
Brittany L
BL
Moyce
Department of Pharmacology & Therapeutics.|Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Research Theme.|Children's Hospital Research Institute of Manitoba.
Laura K
LK
Cole
Department of Pharmacology & Therapeutics.|Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Research Theme.|Children's Hospital Research Institute of Manitoba.
Grant M
GM
Hatch
Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Research Theme.|Children's Hospital Research Institute of Manitoba.|Department of Physiology and Pathophysiology.
Christine A
CA
Doucette
Diagnostic Services of Manitoba, Winnipeg, MB, Canada.
Julianne
J
Klein
Department of Human Nutrition, University of Manitoba, Winnipeg, MB, Canada.
Michel
M
Aliani
Department of Pharmacology & Therapeutics.|Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Research Theme.|Children's Hospital Research Institute of Manitoba.
Vernon W
VW
Dolinsky
D000818:Animals; D016640:Diabetes, Gestational / Q000209:etiology / Q000378:metabolism*; D059305:Diet, High-Fat / Q000009:adverse effects; D004075:Diglycerides / Q000378:metabolism; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism*; D005260:Female; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D055442:Metabolome; D009765:Obesity / Q000209:etiology / Q000378:metabolism*; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013395:Sucrose / Q000633:toxicity
D004075:Diglycerides; D047493:PPAR alpha; D010714:Phosphatidylethanolamines; C483858:phosphatidylethanolamine; D013395:Sucrose