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. 2016 Mar;55(2):589-599. doi: 10.1007/s00394-015-0879-0. Epub 2015 Mar 19.

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.

Keywords: Hamster; Maternal nutrition; Metabolic syndrome; Sphingolipids; n-3 PUFA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Animals
  • Antigens, CD / blood
  • Blood Glucose / metabolism
  • Ceramides / metabolism
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Cricetinae
  • Diacylglycerol O-Acyltransferase / genetics
  • Diacylglycerol O-Acyltransferase / metabolism
  • Diet, High-Fat
  • Dietary Supplements*
  • Fatty Acid Synthases / genetics
  • Fatty Acid Synthases / metabolism
  • Fatty Acids, Omega-3 / pharmacology*
  • Female
  • Hypertriglyceridemia / diet therapy*
  • Lactosylceramides / blood
  • Lipogenesis / drug effects
  • Liver / drug effects*
  • Liver / metabolism
  • Lysophospholipids / metabolism
  • Male
  • Maternal Nutritional Physiological Phenomena*
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sphingolipids / blood
  • Sphingosine / analogs & derivatives
  • Sphingosine / metabolism
  • Stearoyl-CoA Desaturase / genetics
  • Stearoyl-CoA Desaturase / metabolism
  • Sterol Regulatory Element Binding Protein 1 / genetics
  • Sterol Regulatory Element Binding Protein 1 / metabolism
  • Triglycerides / blood
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antigens, CD
  • Blood Glucose
  • Ceramides
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Fatty Acids, Omega-3
  • Lactosylceramides
  • Lysophospholipids
  • RNA, Messenger
  • Sphingolipids
  • Sterol Regulatory Element Binding Protein 1
  • Triglycerides
  • Tumor Necrosis Factor-alpha
  • sphingosine 1-phosphate
  • CDw17 antigen
  • Stearoyl-CoA Desaturase
  • Diacylglycerol O-Acyltransferase
  • Fatty Acid Synthases
  • Sphingosine