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Maternal High-Fat-Diet Programs Rat Offspring Liver Fatty Acid Metabolism

  • Original Article
  • Published:
Lipids

Abstract

In offspring exposed in utero to a maternal diet high in fat (HF), we have previously demonstrated that despite similar birth weights, HF adult offspring at 6 months of age had significantly higher body weights, greater adiposity, and increased triacylglycerol (TAG) levels as compared to controls. We hypothesized that a maternal HF diet predisposes to offspring adiposity via a programmed increase in the synthesis of monounsaturated fatty acids in the liver and hence increased substrate availability for liver TAG synthesis. We further hypothesized that programmed changes in offspring liver fatty acid metabolism are associated with increased liver expression of the lipogenic enzyme stearoyl-CoA desaturase-1 (SCD-1). Female rats were maintained on a HF diet rich in monounsaturated fatty acids (MUFA) prior to and throughout pregnancy and lactation. After birth, newborns were nursed by the same dam, and all offspring were weaned to control diet. Plasma and liver fatty acid compositions were determined using gas chromatography/mass spectrometry. Fatty acid C16 desaturation indices of palmitoleic/palmitic and (vaccenic + palmitoleic)/palmitic and the C18 desaturation index of oleic/stearic were calculated. Liver protein abundance of SCD-1 was analyzed in newborns and adult offspring. Plasma and liver C16 desaturation indices were decreased in HF newborns, but increased in the adult offspring. Liver SCD-1 expression was increased in the HF adult offspring. These data show that the maternal HF diet during pregnancy and lactation increases offspring liver SCD-1 protein abundance and alters the liver C16 desaturase pathway.

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Abbreviations

SCD-1:

Stearoyl-CoA desaturase-1

HF:

High fat

SFA:

Saturated fatty acid

MUFA:

Monounsaturated fatty acids

PUFA:

Polyunsaturated fatty acids

DI:

Desaturation index

E20:

Embryonic day 20

P1:

1 Day of postnatal age

P21:

3 Weeks postnatal age

GC/MS:

Gas chromatography/mass spectrometry

KOH:

Potassium hydroxide

HCl:

Hydrochloric acid

SE:

Standard error

References

  1. Flegal KM, Carroll MD, Kit BK, Ogden CL (2012) Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999–2010. JAMA 307(5):491–497

    Article  PubMed  Google Scholar 

  2. Fisher SC, Kim SY, Sharma AJ, Rochat R, Morrow B (2013) Is obesity still increasing among pregnant women? Pre pregnancy obesity trends in 20 states, 2003–2009. Prev Med 56(6):372–378

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Baeten JM, Bukusi EA, Lambe M (2001) Pregnancy complications and outcomes among overweight and obese nulliparous women. Am J Public Health 91(3):436–440

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Whitaker RC (2004) Predicting preschooler obesity at birth: the role of maternal obesity in early pregnancy. Pediatrics 114(1):e29–e36

    Article  PubMed  Google Scholar 

  5. McMillen IC, Robinson JS (2005) Developmental origins of the metabolic syndrome: prediction, plasticity, and programming. Physiol Rev 85(2):571–633

    Article  CAS  PubMed  Google Scholar 

  6. Hales CN, Desai M, Ozanne SE (1997) The 35 phenotype hypothesis: how does it look after 5 years? Diabet Med 14(3):189–195

    Article  CAS  PubMed  Google Scholar 

  7. Dulloo AG, Jacquet J, Seydoux J, Montani JP (2006) The thrifty ‘catch-up fat’ phenotype: its impact on insulin sensitivity during growth trajectories to obesity and metabolic syndrome. Int J Obes (Lond) 30(Suppl 4):S23–S35

    Article  CAS  Google Scholar 

  8. Hull HR, Thornton JC, Ji Y, Paley C, Rosenn B, Mathews P, Navder K, Yu A, Dorsey K, Gallagher D (2011) Higher infant body fat with excessive gestational weight gain in overweight women. Am J Obstet Gynecol 205(3):211

    Article  PubMed Central  PubMed  Google Scholar 

  9. Boney CM, Verma A, Tucker R, Vohr BR (2005) Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus. Pediatrics 115(3):e290–e296

    Article  PubMed  Google Scholar 

  10. Desai M, Jellyman JK, Han G, Beall M, Lane RH, Ross MG (2014) Rat maternal obesity and high-fat diet program offspring metabolic syndrome. Am J Obstet Gynecol 211(3):237e1

    Article  Google Scholar 

  11. Guberman C, Jellyman JK, Han G, Ross MG, Desai M (2013) Maternal high-fat diet programs rat offspring hypertension and activates the adipose renin-angiotensin system. Am J Obstet Gynecol 209(3):262

    Article  PubMed Central  PubMed  Google Scholar 

  12. Schack-Nielsen L, Michaelsen KF, Gamborg M, Mortensen EL, Sørensen TI (2010) Gestational weight gain in relation to offspring body mass index and obesity from infancy through adulthood. Int J Obes (Lond) 34(1):67–74

    Article  CAS  Google Scholar 

  13. Miyazaki M, Kim YC, Ntambi JM (2001) A lipogenic diet in mice with a disruption of the stearoyl-CoA desaturase 1 gene reveals a stringent requirement of endogenous monounsaturated fatty acids for triglyceride synthesis. J Lipid Res 42(7):1018–1024

    CAS  PubMed  Google Scholar 

  14. Yee JK, Mao CS, Hummel HS, Lim S, Sugano S, Rehan VK, Xiao G, Lee WN (2008) Compartmentalization of stearoyl-coenzyme A desaturase 1 activity in HepG2 cells. J Lipid Res 49(10):2124–2134

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Enoch HG, Catalá A, Strittmatter P (1976) Mechanism of rat liver microsomal stearyl-CoA desaturase. Studies of the substrate specificity, enzyme-substrate interactions, and the function of lipid. J Biol Chem 251(16):5095–5103

    CAS  PubMed  Google Scholar 

  16. Jeyakumar SM, Lopamudra P, Padmini S, Balakrishna N, Giridharan NV, Vajreswari A (2009) Fatty acid desaturation index correlates with body mass and adiposity indices of obesity in Wistar NIN obese mutant rat strains WNIN/Ob and WNIN/GR-Ob. Nutr Metab (Lond) 6:27

    Article  Google Scholar 

  17. Peter A, Cegan A, Wagner S, Lehmann R, Stefan N, Königsrainer A, Königsrainer I, Häring HU, Schleicher E (2009) Hepatic lipid composition and stearoyl-coenzyme A desaturase 1 mRNA expression can be estimated from plasma VLDL fatty acid ratios. Clin Chem 55(12):2113–2120

    Article  CAS  PubMed  Google Scholar 

  18. Vessby B, Gustafsson IB, Tengblad S, Berglund L (2013) Indices of fatty acid desaturase activity in healthy human subjects: effects of different types of dietary fat. Br J Nutr 110(5):871–879

    Article  CAS  PubMed  Google Scholar 

  19. Warensjö E, Rosell M, Hellenius ML, Vessby B, De Faire U, Risérus U (2009) Associations between estimated fatty acid desaturase activities in serum lipids and adipose tissue in humans: links to obesity and insulin resistance. Lipids Health Dis 8:37

    Article  PubMed Central  PubMed  Google Scholar 

  20. Sjögren P, Sierra-Johnson J, Gertow K, Rosell M, Vessby B, de Faire U, Hamsten A, Hellenius ML, Fisher RM (2008) Fatty acid desaturases in human adipose tissue: relationships between gene expression, desaturation indexes and insulin resistance. Diabetologia 51(2):328–335

    Article  PubMed  Google Scholar 

  21. Yee JK, Mao CS, Ross MG, Lee WN, Desai M, Toda A, Kjos SL, Hicks RA, Patterson ME (2014) High oleic/stearic fatty-acid desaturation index in cord plasma from infants of mothers with gestational diabetes. J Perinatol 34(5):357–363

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Cooke PS, Naaz A (2004) Role of estrogens in adipocyte development and function. Exp Biol Med (Maywood) 229(11):1127–1135

    CAS  Google Scholar 

  23. Desai M, Han Guang, Ferelli M, Kallichanda N, Lane RH (2008) Programmed upregulation of adipogenic transcription factors in intrauterine growth-restricted offspring. Reprod Sci 15(8):785–796

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Sardesai V (2011) Introduction to clinical nutrition, 3rd edn. Taylor and Francis Group, Florida

    Google Scholar 

  25. Chong MF, Hodson L, Bickerton AS, Roberts R, Neville M, Karpe F, Frayn KN, Fielding BA (2008) Parallel activation of de novo lipogenesis and stearoyl-CoA desaturase activity after 3 days of high-carbohydrate feeding. Am J Clin Nutr 87(4):817–823

    CAS  PubMed  Google Scholar 

  26. Yee JK, Lee WN, Han G, Ross MG, Desai M (2011) Organ-specific alterations in fatty acid de novo synthesis and desaturation in a rat model of programmed obesity. Lipids Health Dis 10:72

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Benkalfat NB, Merzouk H, Bouanane S, Merzouk SA, Bellenger J, Gresti J, Tessier C, Narce M (2011) Altered adipose tissue metabolism in offspring of dietary obese rat dams. Clin Sci (Lond) 121(1):19–28

    Article  CAS  Google Scholar 

  28. Hodson L, Fielding BA (2013) Stearoyl-CoA desaturase: rogue or innocent bystander? Prog Lipid Res 52(1):15–42

    Article  CAS  PubMed  Google Scholar 

  29. Guo F, Jen KL (1995) High-fat feeding during pregnancy and lactation affects offspring metabolism in rats. Physiol Behav 57(4):681–686

    Article  CAS  PubMed  Google Scholar 

  30. Srinivasan M, Katewa SD, Palaniyappan A, Pandya JD, Patel MS (2006) Maternal high-fat diet consumption results in fetal mal programming predisposing to the onset of metabolic syndrome-like phenotype in adulthood. Am J Physiol Endocrinol Metab 291(4):E792–E799

    Article  CAS  PubMed  Google Scholar 

  31. Ntambi JM, Miyazaki M, Stoehr JP, Lan H, Kendziorski CM, Yandell BS, Song Y, Cohen P, Friedman JM, Attie AD (2002) Loss of stearoyl-CoA desaturase-1 function protects mice against adiposity. Proc Natl Acad Sci USA 99(17):11482–11486

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Kotronen A, Seppänen-Laakso T, Westerbacka J, Kiviluoto T, Arola J, Ruskeepää AL, Yki-Järvinen H, Oresic M (2010) Comparison of lipid and fatty acid composition of the liver, subcutaneous and intra-abdominal adipose tissue, and serum. Obesity (Silver Spring) 18(5):937–944

    Article  CAS  Google Scholar 

  33. Chu K, Miyazaki M, Man WC, Ntambi JM (2006) Stearoyl-coenzyme A desaturase 1 deficiency protects against hypertriglyceridemia and increases plasma high-density lipoprotein cholesterol induced by liver X receptor activation. Mol Cell Biol 26(18):6786–6798

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Guéant JL, Elakoum R, Ziegler O, Coelho D, Feigerlova E, Daval JL, Guéant-Rodriguez RM (2014) Nutritional models of foetal programming and nutrigenomic and epigenomic dysregulations of fatty acid metabolism in the liver and heart. Pflugers Arch 466(5):833–850

    Article  PubMed  Google Scholar 

  35. Bringhenti I, Ornellas F, Martins MA, Mandarim-de-Lacerda CA, Aguila MB (2015) Early hepatic insult in the offspring of obese maternal mice. Nutr Res 35(2):136–145

    Article  CAS  PubMed  Google Scholar 

  36. Brandorff NP (1980) The effect of dietary fat on the fatty acid composition of lipids secreted in rats milk. Lipids 15(4):276–278

    Article  CAS  PubMed  Google Scholar 

  37. Rodríguez-Cruz M, Sánchez R, Bernabe-Garcia R, Maldonado J, Del Prado M, López-Alarcón M (2009) Effect of dietary levels of corn oil on maternal arachidonic acid synthesis and fatty acid composition in lactating rats. Nutrition 25(2):209–215

    Article  PubMed  Google Scholar 

  38. Purcell RH, Sun B, Pass LL, Power ML, Moran TH, Tamashiro KL (2011) Maternal stress and high-fat diet effect on maternal behavior, milk composition, and pup ingestive behavior. Physiol Behav 104(3):474–479

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Mingrone G, Manco M, Mora ME, Guidone C, Iaconelli A, Gniuli D, Leccesi L, Chiellini C, Ghirlanda G (2008) Influence of maternal obesity on insulin sensitivity and secretion in offspring. Diabetes Care 31(9):1872–1876

    Article  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

We thank Stacy Behare for her assistance in animal husbandry and tissue retrieval. We are grateful to Dr. Wai-Nang Paul Lee for his support and guidance with fatty acid analysis. This work was supported by the National Institutes of Health Grants R01DK081756 and R01HD054751. Fatty acid analyses were performed at the Biomedical Mass Spectrometry Facility, supported by UCLA CTSI Grant UL1TR000124, at the Los Angeles Biomedical Research Institute at Harbor-UCLA.

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The authors report no conflict of interest.

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Correspondence to Mina Desai.

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Seet, E.L., Yee, J.K., Jellyman, J.K. et al. Maternal High-Fat-Diet Programs Rat Offspring Liver Fatty Acid Metabolism. Lipids 50, 565–573 (2015). https://doi.org/10.1007/s11745-015-4018-8

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  • DOI: https://doi.org/10.1007/s11745-015-4018-8

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