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Direct and maternal n-3 long-chain polyunsaturated fatty acid supplementation improved triglyceridemia and glycemia through the regulation of hepatic and muscle sphingolipid synthesis in offspring hamsters fed a high-fat diet

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Abstract

Purpose

We recently reported that direct and maternal supplementation with n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) alleviates the metabolic disturbances in adult hamster pups fed with a high-fat diet (HFD). In this study, we hypothesized that these results involved a perinatal modulating effect of sphingolipids by n-3 LC-PUFA.

Methods

We studied the effect of direct and maternal n-3 LC-PUFA supplementation on sphingolipid contents in liver and muscle, hepatic triglycerides (TG) secretion and glucose tolerance. Offspring male hamsters born from supplemented (Cω) or unsupplemented (C) mothers were subjected after weaning to a HFD during 16 weeks, without (Cω-HF or C-HF) or with direct supplementation with n-3 LC-PUFA (C-HFω).

Results

Direct supplementation decreased sphingosine, sphinganine and ceramides in liver and decreased sphingosine, sphinganine, sphingosine-1-phosphate (S1P) and ceramides in muscle in C-HFω compared to C-HF (p < 0.05). Maternal supplementation decreased C20 ceramide and lactosylceramide in liver and sphinganine, S1P and lactosylceramide in muscle (p < 0.05). This supplementation tended to decrease glucosylceramide in liver (p < 0.06) and muscle (p < 0.07) in Cω-HF compared to C-HF. Direct supplementation increased glucose tolerance and decreased hepatic TG secretion and hepatic gene expression levels of diacylglycerol O-acyltransferase 2 (DGAT2), sterol regulatory element-binding protein-1c (SREBP-1c), fatty acid synthase, stearoyl-CoA desaturase-1 (SCD1) and tumor necrosis factor α (TNFα). Maternal supplementation decreased basal glycemia and hepatic TG secretion. We observed a positive correlation between hepatic TG secretion and hepatic ceramide (p = 0.0059), and between basal glycemia and hepatic ceramide (p = 0.04) or muscle lactosylceramide contents (p = 0.001).

Conclusion

We observed an improvement of lipids and glucose metabolism in hamster with n-3 LC-PUFA direct supplementation and a decrease in glycemia and hepatic TG secretion with maternal supplementation. These results are probably related to a decrease in both lipogenesis and sphingolipid contents in liver and muscle.

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Abbreviations

ASM:

Acid sphingomyelinase

AUC:

Area under the curve

DGAT2:

Diacylglycerol O-acyltransferase 2

FBG:

Fasting blood glucose

HDL:

High-density lipoprotein

HFD:

High-fat diet

IPGTT:

Intraperitoneal glucose tolerance test

LC-PUFA:

Long-chain polyunsaturated fatty acids

LDL:

Low-density lipoprotein

PPAR α:

Peroxisome proliferator-activated receptor α

SCD1:

Stearoyl-CoA desaturase-1

SR-B1:

Scavenger receptor type B class 1

SREBP-1c:

Sterol regulatory element-binding protein-1c

S1P:

Sphingosine-1-phosphate

SM:

Sphingomyelins

SPT:

Serine palmitoyl transferase

TNFα:

Tumor necrosis factor α

VLDL:

Very low-density lipoprotein

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Acknowledgments

Authors thank Audrey Aguesse and Stéphanie Crossouard for their technical assistance. This work was supported by CRNHO (Centre de Recherche en Nutrition Humaine Ouest, Nantes) and research program NUPEM supported by Region Pays de la Loire. The n-3 LC-PUFA were kindly provided by Pierre Fabre Santé.

Conflict of interest

The authors declared no conflict of interest.

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Authors and Affiliations

  1. INRA, UMR 1280, Physiologie des Adaptations Nutritionnelles, 44000, Nantes, France

    Fatima Kasbi-Chadli, Véronique Ferchaud-Roucher, Michel Krempf & Khadija Ouguerram

  2. CRNH, West Human Nutrition Research Center, CHU, 44093, Nantes, France

    Fatima Kasbi-Chadli, Véronique Ferchaud-Roucher, Michel Krempf & Khadija Ouguerram

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  1. Fatima Kasbi-Chadli
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  2. Véronique Ferchaud-Roucher
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  4. Khadija Ouguerram
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Correspondence to Khadija Ouguerram.

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Kasbi-Chadli, F., Ferchaud-Roucher, V., Krempf, M. et al. Direct and maternal n-3 long-chain polyunsaturated fatty acid supplementation improved triglyceridemia and glycemia through the regulation of hepatic and muscle sphingolipid synthesis in offspring hamsters fed a high-fat diet. Eur J Nutr 55, 589–599 (2016). https://doi.org/10.1007/s00394-015-0879-0

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