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A gestational ketogenic diet alters maternal metabolic status as well as offspring physiological growth and brain structure in the neonatal mouse.

Sussman D, Ellegood J, Henkelman M - BMC Pregnancy Childbirth (2013)

Bottom Line: To date, no studies have thoroughly investigated the effect of a gestational KD on offspring growth.An anatomical comparison of their brains further revealed significant structural differences at P11.5, and particularly at P21.5.The KD brain shows a relative bilateral decrease in the cortex, fimbria, hippocampus, corpus callosum and lateral ventricle, but a relative volumetric enlargement of the hypothalamus and medulla.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Canada. dafna.sussman@utoronto.ca.

ABSTRACT

Background: The use of the ketogenic diet (KD) among women of child-bearing age has been increasing, leading to increased interest in identifying the diet's suitability during gestation. To date, no studies have thoroughly investigated the effect of a gestational KD on offspring growth. Since ketones have been reported to play a role in cerebral lipid and myelin synthesis, it is particularly important to investigate the diet's impact on brain anatomy of the offspring.

Methods: To fill this knowledge gap we imaged CD-1 mouse neonates whose mothers were fed either a standard diet (SD) or a KD prior to and during gestation. Images were collected at postnatal (P) 11.5 and 21.5 using Magnetic Resonance Imaging (MRI). Maternal metabolic status was also tracked during lactation, by following their body weight, blood glucose, ketone, cholesterol, and triglyceride concentrations.

Results: The KD dams exhibit a significant reduction in maternal fertility and litter size, as well as a high risk of developing fatal ketoacidosis by mid-lactation. To increase survival of the KD dams and offspring, fostering of P2.5 pups (from both KD and SD litters) by SD-foster dams was carried out. This resulted in stabilization of blood ketones of the KD dams, and aversion of the fatal ketoacidosis. We also note a slower and smaller weight loss for the KD compared with the SD dams. The average fostered KD pup exhibits retarded growth by P21.5 compared with the average fostered SD pup. An anatomical comparison of their brains further revealed significant structural differences at P11.5, and particularly at P21.5. The KD brain shows a relative bilateral decrease in the cortex, fimbria, hippocampus, corpus callosum and lateral ventricle, but a relative volumetric enlargement of the hypothalamus and medulla.

Conclusion: A gestational ketogenic diet deleteriously affects maternal fertility and increases susceptibility to fatal ketoacidosis during lactation. Prenatal and early postnatal exposure to a ketogenic diet also results in significant alterations to neonatal brain structure, and results in retarded physiological growth. These alterations could be accompanied by functional and behavioural changes in later postnatal life.

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Average weight-gain per litter of Adopted KD, Adopted SD, and Biological SD pups between P2.5 and P20.5. (Number of litters: NSD−Adopted = 7, NKD−Adopted = 8, NSD−Biological = 15).
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Figure 6: Average weight-gain per litter of Adopted KD, Adopted SD, and Biological SD pups between P2.5 and P20.5. (Number of litters: NSD−Adopted = 7, NKD−Adopted = 8, NSD−Biological = 15).

Mentions: The similarity between the weight gain of the adopted and biological SD pups is also evident in the average weight gain of the pups between P2.5 and P20.5, as show in Figure 6. Figure 6 further shows a smaller weight gain of the adopted KD pups compared with both the adopted and biological SD pups during the first 3 weeks of postnatal life (p <0.05).


A gestational ketogenic diet alters maternal metabolic status as well as offspring physiological growth and brain structure in the neonatal mouse.

Sussman D, Ellegood J, Henkelman M - BMC Pregnancy Childbirth (2013)

Average weight-gain per litter of Adopted KD, Adopted SD, and Biological SD pups between P2.5 and P20.5. (Number of litters: NSD−Adopted = 7, NKD−Adopted = 8, NSD−Biological = 15).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4231349&req=5

Figure 6: Average weight-gain per litter of Adopted KD, Adopted SD, and Biological SD pups between P2.5 and P20.5. (Number of litters: NSD−Adopted = 7, NKD−Adopted = 8, NSD−Biological = 15).
Mentions: The similarity between the weight gain of the adopted and biological SD pups is also evident in the average weight gain of the pups between P2.5 and P20.5, as show in Figure 6. Figure 6 further shows a smaller weight gain of the adopted KD pups compared with both the adopted and biological SD pups during the first 3 weeks of postnatal life (p <0.05).

Bottom Line: To date, no studies have thoroughly investigated the effect of a gestational KD on offspring growth.An anatomical comparison of their brains further revealed significant structural differences at P11.5, and particularly at P21.5.The KD brain shows a relative bilateral decrease in the cortex, fimbria, hippocampus, corpus callosum and lateral ventricle, but a relative volumetric enlargement of the hypothalamus and medulla.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Canada. dafna.sussman@utoronto.ca.

ABSTRACT

Background: The use of the ketogenic diet (KD) among women of child-bearing age has been increasing, leading to increased interest in identifying the diet's suitability during gestation. To date, no studies have thoroughly investigated the effect of a gestational KD on offspring growth. Since ketones have been reported to play a role in cerebral lipid and myelin synthesis, it is particularly important to investigate the diet's impact on brain anatomy of the offspring.

Methods: To fill this knowledge gap we imaged CD-1 mouse neonates whose mothers were fed either a standard diet (SD) or a KD prior to and during gestation. Images were collected at postnatal (P) 11.5 and 21.5 using Magnetic Resonance Imaging (MRI). Maternal metabolic status was also tracked during lactation, by following their body weight, blood glucose, ketone, cholesterol, and triglyceride concentrations.

Results: The KD dams exhibit a significant reduction in maternal fertility and litter size, as well as a high risk of developing fatal ketoacidosis by mid-lactation. To increase survival of the KD dams and offspring, fostering of P2.5 pups (from both KD and SD litters) by SD-foster dams was carried out. This resulted in stabilization of blood ketones of the KD dams, and aversion of the fatal ketoacidosis. We also note a slower and smaller weight loss for the KD compared with the SD dams. The average fostered KD pup exhibits retarded growth by P21.5 compared with the average fostered SD pup. An anatomical comparison of their brains further revealed significant structural differences at P11.5, and particularly at P21.5. The KD brain shows a relative bilateral decrease in the cortex, fimbria, hippocampus, corpus callosum and lateral ventricle, but a relative volumetric enlargement of the hypothalamus and medulla.

Conclusion: A gestational ketogenic diet deleteriously affects maternal fertility and increases susceptibility to fatal ketoacidosis during lactation. Prenatal and early postnatal exposure to a ketogenic diet also results in significant alterations to neonatal brain structure, and results in retarded physiological growth. These alterations could be accompanied by functional and behavioural changes in later postnatal life.

Show MeSH
Related in: MedlinePlus