Hostname: page-component-586b7cd67f-vdxz6 Total loading time: 0 Render date: 2024-11-23T05:31:26.611Z Has data issue: false hasContentIssue false
  • English
  • Français

In rats gestational iron deficiency does not change body fat or hepatic mitochondria in the aged offspring

Published online by Cambridge University Press:  05 September 2017

W. D. Rees ,
S. M. Hay ,
H. E. Hayes ,
C. Birgovan  and
H. J. McArdle
W. D. Rees*
Affiliation:
The Rowett Institute of Nutrition and Health, The University of Aberdeen, Foresterhill, Aberdeen, Scotland, UK.
S. M. Hay
Affiliation:
The Rowett Institute of Nutrition and Health, The University of Aberdeen, Foresterhill, Aberdeen, Scotland, UK.
H. E. Hayes
Affiliation:
The Rowett Institute of Nutrition and Health, The University of Aberdeen, Foresterhill, Aberdeen, Scotland, UK.
C. Birgovan
Affiliation:
The Rowett Institute of Nutrition and Health, The University of Aberdeen, Foresterhill, Aberdeen, Scotland, UK.
H. J. McArdle
Affiliation:
The Rowett Institute of Nutrition and Health, The University of Aberdeen, Foresterhill, Aberdeen, Scotland, UK.
*
*Address for correspondence: W. D. Rees, Rowett Institute of Nutrition and Health, University of Aberdeen , Foresterhill, Aberdeen AB21 9SB, UK. (Email [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Mitochondrial dysfunction and resulting changes in adiposity have been observed in the offspring of animals fed a high fat (HF) diet. As iron is an important component of the mitochondria, we have studied the offspring of female rats fed complete (Con) or iron-deficient (FeD) rations for the duration of gestation to test for similar effects. The FeD offspring were ~12% smaller at weaning and remained so because of a persistent reduction in lean tissue mass. The offspring were fed a complete (stock) diet until 52 weeks of age after which some animals from each litter were fed a HF diet for a further 12 weeks. The HF diet increased body fat when compared with animals fed the stock diet, however, prenatal iron deficiency did not change the ratio of fat:lean in either the stock or HF diet groups. The HF diet caused triglyceride to accumulate in the liver, however, there was no effect of prenatal iron deficiency. The activity of the mitochondrial electron transport complexes was similar in all groups including those challenged with a HF diet. HF feeding increased the number of copies of mitochondrial DNA and the prevalence of the D-loop mutation, however, neither parameter was affected by prenatal iron deficiency. This study shows that the effects of prenatal iron deficiency differ from other models in that there is no persistent effect on hepatic mitochondria in aged animals exposed to an increased metabolic load.

Keywords

high fat dietiron-deficiencyliverpregnancy
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 9 , Issue 2 , April 2018 , pp. 232 - 240
Check for updates
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2017 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Lozoff, B, Klein, NK, Nelson, EC, et al. Behavior of infants with iron-deficiency anemia. Child Dev. 1998; 69, 24–36.Google Scholar
2. Lozoff, B, Jimenez, F, Hagen, J, Mollen, E, Wolf, AW. Poorer behavioral and developmental outcome more than 10 years after treatment for iron deficiency in infancy. Pediatrics. 2000; 105, E51.CrossRefGoogle ScholarPubMed
3. Wachs, TD, Pollitt, E, Cueto, S, Jacoby, E, Creed-Kanashiro, H. Relation of neonatal iron status to individual variability in neonatal temperament. Dev Psychobiol. 2005; 46, 141–153.Google Scholar
4. Lozoff, B, Beard, J, Connor, J, et al. Long-lasting neural and behavioral effects of iron deficiency in infancy. Nutr Rev. 2006; 64(Pt 2), S34–S43.Google Scholar
5. Alwan, NA, Hamamy, H. Maternal iron status in pregnancy and long-term health outcomes in the offspring. J Pediatr Genet. 2015; 4, 111–123.Google Scholar
6. Lill, R, Hoffmann, B, Molik, S, et al. The role of mitochondria in cellular iron-sulfur protein biogenesis and iron metabolism. Biochim Biophys Acta. 2012; 1823, 1491–1508.Google Scholar
7. Borengasser, SJ, Lau, F, Kang, P, et al. Maternal obesity during gestation impairs fatty acid oxidation and mitochondrial SIRT3 expression in rat offspring at weaning. PLoS ONE. 2011; 6, e24068.Google Scholar
8. Borengasser, SJ, Faske, J, Kang, P, et al. In utero exposure to prepregnancy maternal obesity and postweaning high-fat diet impair regulators of mitochondrial dynamics in rat placenta and offspring. Physiol Genomics. 2014; 46, 841–850.Google Scholar
9. Gregorio, BM, Souza-Mello, V, Carvalho, JJ, Mandarim-de-Lacerda, CA, Aguila, MB. Maternal high-fat intake predisposes nonalcoholic fatty liver disease in C57BL/6 offspring. Am J Obstet Gynecol. 2010; 203, 495.e491–495.e498.Google Scholar
10. Elahi, MM, Cagampang, FR, Mukhtar, D, et al. Long-term maternal high-fat feeding from weaning through pregnancy and lactation predisposes offspring to hypertension, raised plasma lipids and fatty liver in mice. Br J Nutr. 2009; 102, 514–519.Google Scholar
11. Bayol, SA, Simbi, BH, Fowkes, RC, Stickland, NC. A maternal ‘junk food’ diet in pregnancy and lactation promotes nonalcoholic fatty liver disease in rat offspring. Endocrinology. 2010; 151, 1451–1461.Google Scholar
12. Bruce, KD, Cagampang, FR, Argenton, M, et al. Maternal high-fat feeding primes steatohepatitis in adult mice offspring, involving mitochondrial dysfunction and altered lipogenesis gene expression. Hepatology. 2009; 50, 1796–1808.Google Scholar
13. Wu, LL, Russell, DL, Wong, SL, et al. Mitochondrial dysfunction in oocytes of obese mothers: transmission to offspring and reversal by pharmacological endoplasmic reticulum stress inhibitors. Development. 2015; 142, 681–691.Google Scholar
14. Walter, PB, Knutson, MD, Paler-Martinez, A, et al. Iron deficiency and iron excess damage mitochondria and mitochondrial DNA in rats. Proc Natl Acad Sci U S A. 2002; 99, 2264–2269.Google Scholar
15. Petersen, KF, Morino, K, Alves, TC, et al. Effect of aging on muscle mitochondrial substrate utilization in humans. Proc Natl Acad Sci U S A. 2015; 112, 11330–11334.Google Scholar
16. Nadal-Casellas, A, Amengual-Cladera, E, Proenza, AM, Llado, I, Gianotti, M. Long-term high-fat-diet feeding impairs mitochondrial biogenesis in liver of male and female rats. Cell Physiol Biochem. 2010; 26, 291–302.Google Scholar
17. Yuzefovych, LV, Musiyenko, SI, Wilson, GL, Rachek, LI. Mitochondrial DNA damage and dysfunction, and oxidative stress are associated with endoplasmic reticulum stress, protein degradation and apoptosis in high fat diet-induced insulin resistance mice. PLoS ONE. 2013; 8, e54059.Google Scholar
18. Gambling, L, Danzeisen, R, Gair, S, et al. Effect of iron deficiency on placental transfer of iron and expression of iron transport proteins in vivo and in vitro. Biochem J. 2001; 356(Pt 3), 883–889.Google Scholar
19. Lobley, GE, Bremner, DM, Holtrop, G, Johnstone, AM, Maloney, C. Impact of high-protein diets with either moderate or low carbohydrate on weight loss, body composition, blood pressure and glucose tolerance in rats. Br J Nutr. 2007; 97, 1099–1108.Google Scholar
20. Maloney, CA, Hay, SM, Reid, MD, et al. A methyl-deficient diet fed to rats during the pre- and peri-conception periods of development modifies the hepatic proteome in the adult offspring. Genes Nutr. 2013; 8, 181–190.Google Scholar
21. McNeil, CJ, Hay, SM, Rucklidge, G, et al. Disruption of lipid metabolism in the liver of the pregnant rat fed folate deficient and methyl donor deficient diets. Br J Nutr. 2008; 99, 262–271.Google Scholar
22. Spinazzi, M, Casarin, A, Pertegato, V, Salviati, L, Angelini, C. Assessment of mitochondrial respiratory chain enzymatic activities on tissues and cultured cells. Nat Protoc. 2012; 7, 1235–1246.Google Scholar
23. Medja, F, Allouche, S, Frachon, P, et al. Development and implementation of standardized respiratory chain spectrophotometric assays for clinical diagnosis. Mitochondrion. 2009; 9, 331–339.Google Scholar
24. Nicklas, JA, Brooks, EM, Hunter, TC, Single, R, Branda, RF. Development of a quantitative PCR (TaqMan) assay for relative mitochondrial DNA copy number and the common mitochondrial DNA deletion in the rat. Environ Mol Mutagen. 2004; 44, 313–320.Google Scholar
25. Bourque, SL, Komolova, M, McCabe, K, Adams, MA, Nakatsu, K. Perinatal iron deficiency combined with a high-fat diet causes obesity and cardiovascular dysregulation. Endocrinology. 2012; 153, 1174–1182.Google Scholar
26. Lewis, RM, Petry, CJ, Ozanne, SE, Hales, CN. Effects of maternal iron restriction in the rat on blood pressure, glucose tolerance, and serum lipids in the 3-month-old offspring. Metabolism. 2001; 50, 562–567.Google Scholar
27. Guéant, J-L, Elakoum, R, Ziegler, O, et al. Nutritional models of foetal programming and nutrigenomic and epigenomic dysregulations of fatty acid metabolism in the liver and heart. Pflügers Arch. 2014; 466, 833–850.Google Scholar
28. Pooya, S, Blaise, S, Moreno Garcia, M, et al. Methyl donor deficiency impairs fatty acid oxidation through PGC-1α hypomethylation and decreased ER-α, ERR-α, and HNF-4α in the rat liver. J Hepatol. 2012; 57, 344–351.Google Scholar
29. Garcia, MM, Guéant-Rodriguez, R-M, Pooya, S, et al. Methyl donor deficiency induces cardiomyopathy through altered methylation/acetylation of PGC-1α by PRMT1 and SIRT1. J Pathol. 2011; 225, 324–335.Google Scholar
30. Komolova, M, Bourque, SL, Nakatsu, K, Adams, MA. Sedentariness and increased visceral adiposity in adult perinatally iron-deficient rats. Int J Obes. 2008; 32, 1441–1444.CrossRefGoogle ScholarPubMed
31. Bertram, C, Trowern, AR, Copin, N, Jackson, AA, Whorwood, CB. The maternal diet during pregnancy programs altered expression of the glucocorticoid receptor and type 2 11β-hydroxysteroid dehydrogenase: potential molecular mechanisms underlying the programming of hypertension in utero. Endocrinology. 2001; 142, 2841–2853.Google Scholar
32. Langley-Evans, SC. Critical differences between two low protein diet protocols in the programming of hypertension in the rat. Int J Food Sci Nutr. 2000; 51, 11–17.Google Scholar
33. Maloney, CA, Lilley, C, Czopek, A, Hay, SM, Rees, WD. Interactions between protein and vegetable oils in the maternal diet determine the programming of the insulin axis in the rat. Br J Nutr. 2007; 97, 912–920.Google Scholar
34. McNeil, CJ, Maloney, CA, Hay, SM, Rees, WD. Sources of dietary protein and lipid interact to modify maternal and fetal development in the pregnant rat. Proc Nutr Soc. 2007; 66, 21A.Google Scholar
35. Hay, SM, McArdle, HJ, Hayes, HE, Stevens, VJ, Rees, WD. The effect of iron deficiency on the temporal changes in the expression of genes associated with fat metabolism in the pregnant rat. Physiol Rep. 2016; 4, e12908.Google Scholar
36. Otera, H, Ishihara, N, Mihara, K. New insights into the function and regulation of mitochondrial fission. Biochim Biophys Acta. 2013; 1833, 1256–1268.Google Scholar
37. Archer, SL. Mitochondrial dynamics – mitochondrial fission and fusion in human diseases. N Engl J Med. 2013; 369, 2236–2251.Google Scholar
38. Flamment, M, Rieusset, J, Vidal, H, et al. Regulation of hepatic mitochondrial metabolism in response to a high fat diet: a longitudinal study in rats. J Physiol Biochem. 2012; 68, 335–344.Google Scholar
39. Lionetti, L, Mollica, MP, Donizzetti, I, et al. High-lard and high-fish-oil diets differ in their effects on function and dynamic behaviour of rat hepatic mitochondria. PLoS ONE. 2014; 9, e92753.Google Scholar
40. Baker, MJ, Lampe, PA, Stojanovski, D, et al. Stress – induced OMA1 activation and autocatalytic turnover regulate OPA1 – dependent mitochondrial dynamics. EMBO J. 2014; 33, 578–593.Google Scholar
41. Gao, X, Campian, JL, Qian, M, Sun, X-F, Eaton, JW. Mitochondrial DNA damage in iron overload. J Biol Chem. 2009; 284, 4767–4775.Google Scholar
42. Williams, RB, Mills, CF. The experimental production of zinc deficiency in the rat. Br J Nutr. 1970; 24, 989–1003.Google Scholar