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Horm Metab Res 2011; 43(3): 178-182
DOI: 10.1055/s-0030-1270528
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Altered Gene Expressions of Ghrelin, PYY, and CCK in the Gastrointestinal Tract of the Hyperphagic Intrauterine Growth Restriction Rat Offspring

E. Nagata1 , Y. Nakagawa1 , R. Yamaguchi1 , Y. Fujisawa1 , S. Sano1 , E. Satake1 , R. Matsushita1 , T. Nakanishi1 , Y. Liu2 , T. Ohzeki1
  • 1Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan
  • 2Division of Endocrinology, Charles R. Drew University of Medicine and Science, UCLA School of Medicine, Los Angeles, California, USA
Further Information

Publication History

received 26.08.2010

accepted 22.12.2010

Publication Date:
24 January 2011 (online)

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Abstract

Intrauterine growth restriction (IUGR) is associated with a substantially greater incidence of metabolic syndrome in adulthood. Animal studies have shown that IUGR offspring are hyperphagic during the early postnatal period and therefore exhibit obesity. The molecular mechanisms underlying food intake regulation in the gastrointestinal tract have not been clarified in IUGR. In the present study, we utilized a rat model of IUGR by restricting the food intake of the mother (50% of the normal intake, ad libitum; FR group) from day 7 of gestation until delivery. Pups from undernourished mothers were fostered by control mothers. We examined the food intake and assessed the gene expressions of ghrelin, peptide YY (PYY), and cholecystokinin (CCK) in the alimentary tract of male newborns (postnatal day1) and adult offspring (age, 7 months). Compared to the offspring whose mothers received the standard diet ad libitum (CON offspring), FR offspring were hyperphagic from the weaning time until the end of the experiment, and resulted in a heavier final weight. Both newborn and adult FR offspring had higher ghrelin gene expression in the stomach and higher ghrelin plasma levels than did the controls. Although the gastrointestinal gene expressions and plasma levels of the anorexic peptides, PYY and CCK, were elevated in the FR newborns, they decreased in the FR adults. Our findings suggest that the altered gene expressions of orexigenic and anorexigenic gut peptides in the gastrointestinal tract in the maternal undernutrition-induced IUGR offspring provide a potential mechanism to explain hyperphagia and obesity seen in these offspring.

Key words

maternal food restriction - obesity - orexigenic gut hormone - anorexigenic gut hormone

References

  • 1 Gluckman PD, Hanson MA. Living with the past: Evolution, development, and patterns of disease.  Science. 2004;  305 1733-1736
    Google Scholar
  • 2 Fujisawa Y, Nakagawa Y, Li R, Ohzeki T. Streptozotocin-induced diabetes in the pregnant rat reduces 11 beta-hydroxysteroid dehydrogenase type 2 expression in placenta and fetal kidney.  Life Sci. 2004;  75 2797-2805
    Google Scholar
  • 3 Fujisawa Y, Nakagawa Y, Li RS, Liu YJ, Ohzeki T. Diabetic pregnancy in rats leads to impaired glucose metabolism in offspring involving tissue-specific dysregulation of 11 beta-hydroxysteroid dehydrogenase type 1 expression.  Life Sci. 2007;  81 724-731
    Google Scholar
  • 4 Murphy VE, Smith R, Giles WB, Clifton VL. Endocrine regulation of human fetal growth: the role of the mother, placenta, and fetus.  Endocr Rev. 2006;  27 141-169
    Google Scholar
  • 5 Jaquet D, Deghmoun S, Chevenne D, Collin D, Czernichow P, Levy-Marchal C. Dynamic change in adiposity from fetal to postnatal life is involved in the metabolic syndrome associated with reduced fetal growth.  Diabetologia. 2005;  48 849-855
    Google Scholar
  • 6 Desai M, Babu J, Ross MG. Programmed metabolic syndrome: prenatal undernutrition and postweaning overnutrition.  Am J Physiol Regul Integr Comp Physiol. 2007;  293 R2306-R2314
    Google Scholar
  • 7 Desai M, Gayle D, Babu J, Ross MG. Programmed obesity in intrauterine growth-restricted newborns: modulation by newborn nutrition.  Am J Physiol Regul Integr Comp Physiol. 2005;  288 R91-R96
    Google Scholar
  • 8 McMillen IC, Adam CL, Muhlhausler BS. Early origins of obesity: programming the appetite regulatory system.  J Physiol. 2005;  565 9-17
    Google Scholar
  • 9 Plagemann A. Perinatal programming and functional teratogenesis: impact on body weight regulation and obesity.  Physiol Behav. 2005;  86 661-668
    Google Scholar
  • 10 Ikenasio-Thorpe BA, Breier BH, Vickers MH, Fraser M. Prenatal influences on susceptibility to diet-induced obesity are mediated by altered neuroendocrine gene expression.  J Endocrinol. 2007;  193 31-37
    Google Scholar
  • 11 Vincent RP, Ashrafian H, le Roux CW. Mechanisms of disease: the role of gastrointestinal hormones in appetite and obesity.  Nat Clin Pract Gastroenterol Hepatol. 2008;  5 268-277
    Google Scholar
  • 12 Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach.  Nature. 1999;  402 656-660
    Google Scholar
  • 13 Nakazato M, Murakami N, Date Y, Kojima M, Matsuo H, Kangawa K, Matsukura S. A role for ghrelin in the central regulation of feeding.  Nature. 2001;  409 194-198
    Google Scholar
  • 14 Adrian TE, Ferri GL, Bacarese-Hamilton AJ, Fuessl HS, Polak JM, Bloom SR. Human distribution and release of a putative new gut hormone, peptide YY.  Gastroenterology. 1985;  89 1070-1077
    Google Scholar
  • 15 Batterham RL, Cowley MA, Small CJ, Herzog H, Cohen MA, Dakin CL, Wren AM, Brynes AE, Low MJ, Ghatei MA, Cone RD, Bloom SR. Gut hormone PYY(3–36) physiologically inhibits food intake.  Nature. 2002;  418 650-654
    Google Scholar
  • 16 Little TJ, Horowitz M, Feinle-Bisset C. Role of cholecystokinin in appetite control and body weight regulation.  Obes Rev. 2005;  6 297-306
    Google Scholar
  • 17 Burdge GC, Hanson MA, Slater-Jefferies JL, Lillycrop KA. Epigenetic regulation of transcription: A mechanism for inducing variations in phenotype (fetal programming) by differences in nutrition during early life?.  Br J Nutr. 2007;  97 1036-1046
    Google Scholar
  • 18 Hayashida T, Nakahara K, Mondal MS, Date Y, Nakazato M, Kojima M, Kangawa K, Murakami N. Ghrelin in neonatal rats: distribution in stomach and its possible role.  J Endocrinol. 2002;  173 239-245
    Google Scholar
  • 19 Haqq AM, Farooqi IS, O’Rahilly S, Stadler DD, Rosenfeld RG, Pratt KL, LaFranchi SH, Purnell JQ. Serum ghrelin levels are inversely correlated with body mass index, age, and insulin concentrations in normal children and are markedly increased in Prader-Willi syndrome.  J Clin Endocrinol Metab. 2003;  88 174-178
    Google Scholar
  • 20 Gomez G, Zhang T, Rajaraman S, Thakore KN, Yanaihara N, Townsend Jr CM, Thompson JC, Greeley GH. Intestinal peptide YY: ontogeny of gene expression in rat bowel and trophic actions on rat and mouse bowel.  Am J Physiol. 1995;  268 G71-G81
    Google Scholar
  • 21 Robinson PH, Moran TH, Goldrich M, McHugh PR. Development of cholecystokinin binding sites in rat upper gastrointestinal tract.  Am J Physiol. 1987;  252 G529-G34
    Google Scholar
  • 22 Brand SJ. The post-natal development of cholecystokinin-like activity in the brain and small intestine of the rat.  J Physiol. 1982;  326 425-433
    Google Scholar
  • 23 Nakahara T, Kojima S, Tanaka M, Yasuhara D, Harada T, Sagiyama K, Muranaga T, Nagai N, Nakazato M, Nozoe S, Naruo T, Inui A. Incomplete restoration of the secretion of ghrelin and PYY compared to insulin after food ingestion following weight gain in anorexia nervosa.  J Psychiatr Res. 2007;  41 814-820
    Google Scholar
  • 24 Tamai H, Takemura J, Kobayashi N, Matsubayashi S, Matsukura S, Nakagawa T. Changes in plasma cholecystokinin concentrations after oral glucose tolerance test in anorexia nervosa before and after therapy.  Metabolism. 1993;  42 581-584
    Google Scholar
  • 25 Batterham RL, Cohen MA, Ellis SM, Le Roux CW, Withers DJ, Frost GS, Ghatei MA, Bloom SR. Inhibition of food intake in obese subjects by peptide YY3-36.  N Engl J Med. 2003;  349 941-948
    Google Scholar
  • 26 Baranowska B, Radzikowska M, Wasilewska-Dziubinska E, Roguski K, Borowiec M. Disturbed release of gastrointestinal peptides in anorexia nervosa and in obesity.  Diabetes Obes Metab. 2000;  2 99-103
    Google Scholar
  • 27 Huda MS, Wilding JP, Pinkney JH. Gut peptides and the regulation of appetite.  Obes Rev. 2006;  7 163-182
    Google Scholar
  • 28 Vickers MH, Breier BH, Cutfield WS, Hofman PL, Gluckman PD. Fetal origins of hyperphagia, obesity, and hypertension and postnatal amplification by hypercaloric nutrition.  Am J Physiol Endocrinol Metab. 2000;  279 E83-E87
    Google Scholar
  • 29 Boersma B, Wit JM. Catch-up growth.  Endocr Rev. 1997;  18 646-661
    Google Scholar

Correspondence

E. Nagata

1-20-1 Handayama

Higashi-ku

431-3192 Hamamatsu

Japan

Phone: +81/53/435 2312

Fax: +81/53/435 2311

Email: amn_e@hama-med.ac.jp

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