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Fish Oil and Cardiac Akt/mTOR-Mediated Insulin Resistance in Infants with Maternal Diabetes

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Nutrition and Diet in Maternal Diabetes

Part of the book series: Nutrition and Health ((NH))

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Abstract

We recently developed an animal model of hyperglycaemia during pregnancy to investigate the molecular mechanisms underlying cardiac abnormalities observed in infants of diabetic mothers (IDMs). Furthermore, we explored the diet that should be consumed to improve the abnormalities by a molecular nutritional study and investigated the potential molecular pathway for this effect in the animal model. Assessment of newborn rat hearts revealed that altered insulin signalling-induced insulin resistance by inhibiting the Akt/mammalian target of rapamycin (mTOR) pathway, which was improved in the offspring of rats that were fed a fish oil-rich diet. Here, we describe the significance of consuming fish oil during pregnancy in the first section of this chapter. The second section deal with the potential molecular pathways involved in EPA-mediated regulation of cardiac function. Studies have demonstrated that intrauterine foetal exposure to hyperglycaemia during pregnancy was associated with cardiovascular complications, such as cardiomyocyte hypertrophy, in infants of diabetic mothers (IDMs). We recently developed an animal model of hyperglycaemia during pregnancy to investigate the molecular mechanisms underlying cardiac abnormalities observed in IDMs. Furthermore, we explored the diet that should be consumed to improve the abnormalities by a molecular nutritional study and investigated the potential molecular pathway for this effect in the animal model. Assessment of newborn rat hearts revealed that altered insulin signalling-induced insulin resistance by inhibiting the Akt/mammalian target of rapamycin (mTOR) pathway, which was improved in the offspring of rats that were fed a fish oil-rich diet. Nevertheless, specific ingredients of fish oil that are responsible for improving abnormal insulin signalling remain unclear. Fish oil is present in many types of seafood, particularly fatty fish, and contains high docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) levels, both of which are omega-3 polyunsaturated fatty acids (PUFAs). Consuming fish oil lowers plasma triglyceride levels, resting heart rate and blood pressure and reduces inflammation and improves vascular function. Consuming EPA is also associated with improvements in patients with cardiovascular diseases. Here, we describe the significance of consuming fish oil during pregnancy in the first section of this chapter. The second section examines the potential molecular pathways involved in EPA-mediated regulation of cardiac function. EPA influences a myriad of molecular signalling pathways by altering the functions of key enzymes via membrane and nuclear receptors and transcription factors and through changes in the eicosanoid profiles. Therefore, EPA may have beneficial effects on foetal heart, providing protection from a hyperglycaemic intrauterine environment in pregnant diabetic mothers.

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Abbreviations

IDMs:

Infants of diabetic mothers

mTOR:

Mammalian target of rapamycin

EPA:

Eicosapentaenoic acid

DHA:

Docosahexaenoic acid

PUFAs:

Polyunsaturated fatty acids

PA:

Palmitic acid

IRS:

Insulin receptor substrate

GLUT4:

Glucose transporter type 4

MAPK:

Mitogen-activated protein kinase

JNK:

C-Jun N-terminal kinase

ET-1:

Endothelin-1

GPCR:

G protein-coupled receptor

HUVEC:

Shuman umbilical vein endothelial cells

TGF-β1:

Transforming growth factor β1

NF-κB:

Nuclear factor κB

TNF-α:

Tumour necrosis factor-α

AMPK:

AMP-activated protein kinase

TAK1:

TGF-β activated kinase-1

FFAR4:

Free fatty acid receptor

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Acknowledgements

This study was partially supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (15K00809 to AN and 26750054 to RK) and a grant from the Smoking Research Foundation (to AN).

Author information

Authors and Affiliations

  1. Department of Molecular Pharmacology and Oncology, School of Medicine, Gunma University, 3-39-22 Showa-Machi, Maebashi, Gunma, 371-8511, Japan

    Akio Nakamura

  2. Department of Nutrition, Faculty of Health and Welfare, Takasaki University of Health and Welfare, 37-1 Nakaorui-Machi, Takasaki, Gunma, 370-0033, Japan

    Ritsuko Kawaharada

Authors
  1. Akio Nakamura
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Correspondence to Akio Nakamura .

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Editors and Affiliations

  1. Department of Nutrition, King’s College London, London, United Kingdom

    Rajkumar Rajendram

  2. Department of Nutrition, King’s College London, London, United Kingdom

    Victor R. Preedy

  3. Department of Biomedical Sciences, University of Westminster, London, United Kingdom

    Vinood B. Patel

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Nakamura, A., Kawaharada, R. (2018). Fish Oil and Cardiac Akt/mTOR-Mediated Insulin Resistance in Infants with Maternal Diabetes. In: Rajendram, R., Preedy, V., Patel, V. (eds) Nutrition and Diet in Maternal Diabetes. Nutrition and Health. Humana Press, Cham. https://doi.org/10.1007/978-3-319-56440-1_14

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  • DOI: https://doi.org/10.1007/978-3-319-56440-1_14

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