Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.736
5-Year Impact Factor – 2.135
Index Copernicus  – 166.39
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2010, vol. 19, nr 3, May-June, p. 301–312

Publication type: original article

Language: English

Both Genders Can Propagate Obesity-Prone-Phenotype Impacting Placental Amino Acid Transport System A Activity in a Rat Model of Gestational Protein Restriction

Przekazywanie w zależności od płci fenotypu skłonności do otyłości wpływającego na czynność układu transportu aminokwasów A w łożysku – na szczurzym modelu

Allah Haafiz1,, Hilton M. Bernstein2,, Mark Beveridge1,, Donald A. Novak1,

1 Division of Pediatric Gastroenterology, Department of Pediatrics, University of Florida, USA

2 Florida Hospital Center for Neonatal Care, Orlando, USA

Abstract

Background. Gestational protein restriction (GPR) can program a fetal phenotype prone to develop metabolic syndrome (MetS) in successive generations.
Objectives. To understand the placental-fetal adaptations underpinning metabolic syndrome (MetS) prone phenotype in successive generations.
Material and Methods. Rats (F0) were pair-fed either a 19% normal protein diet (NPD) or an 8% low protein diet (LPD) through pregnancy and lactation. Male and female offspring (F1) were bred to control animals, and the growth of F2 animals monitored for 15 months. [14C]-2-(methylamino) isobutyric acid) (MeAIB) was used to monitor the activity of placental amino acid transport system A (SysA).
Results. Maternal weight gain (g) in F0 pregnancies of the LPD group was less than the NPD group (105 ± 15 vs. 120 ± 25, p ≤ 0.005). Fetal, 3.8 ± 0.9 g (LPD) vs. 3.7 ± 0.7 g (NPD); p ≤ 0.2, and placental weights, 0.56 ± 0.01 g (LPD) vs. 0.6 ± 0.02 g (NPD); p ≤ 0.6 were comparable. MeAIB transfer expressed as (DPM) of gram fetus/mL maternal serum (0.08 ± 0.010 vs. 0.14 ± 0.02; p ≤ 0.003) and (DPM) gram fetus/DPM gram placenta were lower (0.10 ± 0.01 vs. 0.14 ± 0.01; p ≤ 0.02) in LPD than NPD group. Transport in apical membrane vesicles from LPD group was decreased (15 ± 2 vs. 23 ± 4, pmol·mg–1 protein 10sec–1; p = 0.05). Maternal-fetal MeAIB transfers, fetal and placental weights, and maternal weight gains in F1 pregnancies were comparable between animals descended from NPD and LPD groups. However, F2 generation postnatal weight gains were impacted by F1 gestational nutrition (LPD vs. NPD; p ≤ 0.0001).
Conclusion. Moderate GPR impacted placental nutrient transfer in F0 pregnancies; F2 descended from LPD exposed F1 generation tended to be larger than their NPD derived counterparts through 15 months of age samples.

Streszczenie

Wprowadzenie. Ograniczenie podaży białka w ciąży może wywołać fenotyp skłonności do zespołu metabolicznego u płodu w kolejnych pokoleniach.
Cel pracy. Wyjaśnienie zależności między płodem a łożyskiem wywołujących skłonność do zespołu metabolicznego w kolejnych pokoleniach.
Materiał i metody. U szczurów (F0) podczas ciąży i laktacji zastosowano dietę z 19% prawidłową zawartością białka (NPD) i z 8% małą zawartością białka (LPD). Potomstwo płci męskiej i żeńskiej (F1) krzyżowano ze zwierzętami z grupy kontrolnej. Rozwój zwierząt F2 monitorowano przez 15 miesięcy. Za pomocą kwasu metyloaminoizomasłowego (MeAIB) monitorowano czynność układu transportu aminokwasów w łożysku.
Wyniki. Przyrost masy ciała matek w ciążach F0 w grupie LPD był mniejszy niż w grupie NPD (105 ± 15 vs 120 ± ± 25, p ≤ 0,005). Masa ciała płodów (3,8 ± 0,9 g (LPD) vs 3,7 ± 0,7 g (NPD); p ≤ 0,2) i łożysk (0,56 ± 0,01 g (LPD) vs 0,6 ± 0,02 g (NPD); p ≤ 0,6) były porównywalne. Transport MeAIB wyrażony jako (DPM) gram płodu/mL surowicy matki ((0,08 ± 0,010 vs 0,14 ± 0,02; p ≤ 0,003) i jako (DPM) gram płodu/DPM gram łożyska (0,10 ± 0,01 vs 0,14 ± ± 0,01; p ≤ 0,02) był mniejszy w grupie LPD niż w grupie NPD. Transport w błonie szczytowej pęcherzyków z grupy LPD był mniejszy (15 ± 2 vs 23 ± 4, pmol·mg–1 białka 10 s–1; p = 0,05). Matczyno-płodowy transfer MeAIB, masa płodu i łożyska oraz przyrost masy ciała matek w ciążach F1 były porównywalne między zwierzętami pochodzącymi z grupy NPD i LPD. Na przyrost masy ciała po urodzeniu w pokoleniu F2 miało wpływ żywienie w ciąży w pokoleniu F1 (LPD vs NPD; p ≤ 0,0001).
Wnioski. Umiarkowane ograniczenie podaży białka w ciąży wpłynęło na łożyskowy transport składników odżywczych w ciążach F0. Zwierzęta F2 pochodzące z pokolenia LPD F1 były większe niż osobniki po NPD w wieku 15 miesięcy.

Key words

nutrient gene interaction, fetal programming, fetal origins of adult disease, metabolic syndrome

Słowa kluczowe

interakcje genów składników odżywczych, programowanie płodu, płodowe pochodzenie chorób wieku dorosłego, zespół metaboliczny

References (30)

  1. Roseboom TJ, van der Meulen JH, Osmond C, Barker DJ, Ravelli AC, Schroeder-Tanka JM et al.: Coronary heart disease after prenatal exposure to the Dutch famine, 1944–1945. Heart 2000 Dec, 84(6), 595–598.
  2. Hales CN, Barker DJ: Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia 1992 Jul, 35(7), 595–601.
  3. Wilson PW, Grundy SM: The metabolic syndrome: practical guide to origins and treatment: Part I. Circulation 2003 Sep 23, 108(12), 1422–1424.
  4. Meigs JB, Wilson PW, Nathan DM, D’Agostino RB, Sr, Williams K, Haffner SM: Prevalence and characteristics of the metabolic syndrome in the San Antonio Heart and Framingham Offspring Studies. Diabetes 2003, 52(8), 2160–2167.
  5. Balkau B, Charles MA, Drivsholm T, Borch-Johnsen K, Wareham N, Yudkin JS, et al.: Frequency of the WHO metabolic syndrome in European cohorts, and an alternative definition of an insulin resistance syndrome. Diabetes Metab 2002 Nov, 28(5), 364–376.
  6. Haffner S, Taegtmeyer H: Epidemic obesity and the metabolic syndrome. Circulation 2003 Sep 30, 108(13), 1541–1545.
  7. Malandro MS, Beveridge MJ, Kilberg MS, Novak DA: Effect of low-protein diet-induced intrauterine growth retardation on rat placental amino acid transport. Am J Physiol Cell Physiol 1996 Jul 1, 271(1), C295–C303.
  8. Jansson N, Pettersson J, Haafiz A, Ericsson A, Palmberg I, Tranberg M et al.: Down-regulation of placental transport of amino acids precedes the development of intrauterine growth restriction in rats fed a low protein diet. J Physiol 2006 Nov 1, 576(Pt 3), 935–946.
  9. Malandro MS, Beveridge MJ, Kilberg MS: Effect of a low-protein diet induced intrauterine growth retardation in rat placental amino acid transport. Am J Physiol 1996, 271, C295–C303.
  10. Novak DA, Beveridge MJ, Malandro M, Seo J: Ontogeny of amino acid transport system A in rat placenta. Placenta 1996 Nov, 17, 643–651.
  11. Malandro MS, Beveridge MJ, Kilberg MS, Novak DA: Effect of low-protein diet-induced intrauterine growth retardation on rat placental amino acid transport. Am J Physiol Cell Physiol 1996 Jul 1, 271(1), C295–C303.
  12. Malandro MS, Beveridge MJ, Kilberg MS, Novak DA: Ontogeny of cationic amino acid transport systems in rat placenta. Am J Physiol 1994, 267, C804–C811.
  13. Novak DA, Beveridge MJ, Malandro M, Seo J: Ontogeny of amino acid transport system A in rat placenta. Placenta 1996 Nov, 17, 643–651.
  14. Glazier JD, Jones CJ, Sibley CP: Preparation of plasma membrane vesicles from the rat placenta at term and measurement of Na+ uptake. Placenta 1990 Sep, 11(5), 451–463.
  15. Novak DA, Beveridge MJ, Malandro M, Seo J: Ontogeny of amino acid transport system A in rat placenta. Placenta 1996 Nov, 17, 643–651.
  16. Malandro MS, Beveridge MJ, Kilberg MS, Novak DA: Effect of low-protein diet-induced intrauterine growth retardation on rat placental amino acid transport. Am J Physiol Cell Physiol 1996 Jul 1, 271(1), C295–C303.
  17. Desai M, Crowther NJ, Lucas A, Hales CN: Organ-selective growth in the offspring of protein-restricted mothers. Br J Nutr 1996 Oct, 76(4), 591–603.
  18. Benyshek DC, Johnston CS, Martin JF: Post-natal diet determines insulin resistance in fetally malnourished, low birthweight rats (F1) but diet does not modify the insulin resistance of their offspring (F2). Life Sci 2004 Apr 30, 74(24), 3033–3041.
  19. Zambrano E, Martinez-Samayoa PM, Bautista CJ, Deas M, Guillen L, Rodriguez-Gonzalez GL et al.: Sex differences in transgenerational alterations of growth and metabolism in progeny (F2) of female offspring (F1) of rats fed a low protein diet during pregnancy and lactation. J Physiol 2005 Apr 28, 566(Pt 1), 225–236.
  20. Malandro MS, Beveridge MJ, Kilberg MS, Novak DA: Effect of low-protein diet-induced intrauterine growth retardation on rat placental amino acid transport. Am J Physiol Cell Physiol 1996 Jul 1, 271(1), C295–C303.
  21. Jansson N, Pettersson J, Haafiz A, Ericsson A, Palmberg I, Tranberg M et al.: Down-regulation of placental transport of amino acids precedes the development of intrauterine growth restriction in rats fed a low protein diet. J Physiol 2006 Nov 1, 576(Pt 3), 935–946.
  22. Berney DM, Desai M, Palmer DJ, Greenwald S, Brown A, Hales CN et al.: The effects of maternal protein deprivation on the fetal rat pancreas: major structural changes and their recuperation. J Pathol 1997 Sep, 183(1), 109–115.
  23. Desai M, Crowther NJ, Lucas A, Hales CN: Organ-selective growth in the offspring of protein-restricted mothers. Br J Nutr 1996 Oct, 76(4), 591–603.
  24. Ghusain-Choueiri AA, Rath EA: Effect of carbohydrate source on lipid metabolism in lactating mice and on pup development. Br J Nutr 1995 Dec, 74(6), 821–831.
  25. Turner MR, Bryant JS: Insulin secretion in young and adult offspring of rats given diets of varying protein and sucrose content during pregnancy and lactation [proceedings]. Proc Nutr Soc 1976 Dec, 35(3), 123A–124A.
  26. Hales CN, Ozanne SE: For Debate: Fetal and early postnatal growth restriction lead to diabetes, the metabolic syndrome and renal failure. Diabetologia 2003, 46(7), 1013–1019.
  27. Sugden MC, Holness MJ: Gender-specific programming of insulin secretion and action. J Endocrinol 2002 Dec, 175(3), 757–767.
  28. Desai M, Hales CN: Role of fetal and infant growth in programming metabolism in later life. Biol Rev Camb Philos Soc 1997 May, 72(2), 329–348.
  29. Zambrano E, Martinez-Samayoa PM, Bautista CJ, Deas M, Guillen L, Rodriguez-Gonzalez GL et al.: Sex differences in transgenerational alterations of growth and metabolism in progeny (F2) of female offspring (F1) of rats fed a low protein diet during pregnancy and lactation. J Physiol 2005 Apr 28, 566(Pt 1), 225–236.
  30. Benyshek DC, Johnston CS, Martin JF: Post-natal diet determines insulin resistance in fetally malnourished, low birthweight rats (F1) but diet does not modify the insulin resistance of their offspring (F2). Life Sci 2004 Apr 30, 74(24), 3033–3041.