Abstract
BackgroundGestational diabetes is associated with increased risk of type 2 diabetes mellitus and cardiovascular disease for the mother in the decade after delivery. However, the molecular mechanisms that drive these effects are unknown. Recent studies in humans have shown that lipid metabolism is dysregulated before diagnosis of and during gestational diabetes and we have shown previously that lipid metabolism is also altered in obese female mice before, during and after pregnancy. These observations led us to the hypothesis that this persistent dysregulation reflects an altered control of lipid distribution throughout the organism.MethodsWe tested this in post-weaning (PW) dams using our established mouse model of obese GDM (high fat, high sugar, obesogenic diet) and an updated purpose-built computational tool for plotting the distribution of lipid variables throughout the maternal system (Lipid Traffic Analysis v2.3).ResultsThis network analysis showed that unlike hyperglycaemia, lipid distribution and traffic do not return to normal after pregnancy in obese mouse dams. A greater range of phosphatidylcholines was found throughout the lean compared to obese post-weaning dams. A range of triglycerides that were found in the hearts of lean post-weaning dams were only found in the livers of obese post-weaning dams and the abundance of odd-chain FA-containing lipids differed locally in the two groups. We have therefore shown that the control of lipid distribution changed for several metabolic pathways, with evidence for changes to the regulation of phospholipid biosynthesis and FA distribution, in a number of tissues.ConclusionsWe conclude that the control of lipid metabolism is altered following an obese pregnancy. These results support the hypothesis that obese dams that developed GDM maintain dysregulated lipid metabolism after pregnancy even when glycaemia returned to normal, and that these alterations could contribute to the increased risk of later type 2 diabetes and cardiovascular disease.
Highlights
Gestational diabetes mellitus (GDM) is the most common complication of pregnancy and is known to be associated with an increased risk of metabolic disease post partum
Mouse model of gestational diabetes Glucose tolerance tests showed that the lean (Control) and obeseGDM dams displayed similar glycaemic control post partum (Fig. 2A, B)
The aim of this study was to test the hypothesis that changes in control of lipid metabolism outlast the hyperglycaemia associated with GDM
Summary
Gestational diabetes mellitus (GDM) is the most common complication of pregnancy and is known to be associated with an increased risk of metabolic disease post partum. Most of the variables identified had several olefin bonds, indicating that the supply and distribution of polyunsaturated fatty acids may be important As this dysregulation of lipid metabolism in humans occurs 10 weeks before diagnosis of gestational diabetes and includes alterations in the metabolism of both structural lipids and triglycerides, the evidence suggests there are systemic dysregulations in lipid metabolism that could contribute to the development of GDM. CONCLUSIONS: We conclude that the control of lipid metabolism is altered following an obese pregnancy These results support the hypothesis that obese dams that developed GDM maintain dysregulated lipid metabolism after pregnancy even when glycaemia returned to normal, and that these alterations could contribute to the increased risk of later type 2 diabetes and cardiovascular disease
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