Effect of Neonatal Hypoxia on Leptin, Insulin, Growth Hormone and Body Composition in the Rat

The purpose of the present study was to evaluate the effect of exposure to hypoxia from birth to 7 days of age on leptin, insulin, growth hormone (GH), insulin-like growth factor-1 (IGF-1), glucose, corticosterone, body weight, and body composition in rats studied at 7 days of age and then after return to normoxia. Hypoxia for the first 7 days of life resulted in a significant decrease in plasma leptin, body weight, and an increase in corticosterone and insulin with no change in plasma glucose, GH or IGF-1. There was no significant effect of hypoxia on % lean body mass, but a small but significant increase in % body fat. Bone mineral density (BMD) was lower in 7-day-old hypoxic rats as compared to normoxic controls. All hormonal variables and BMD had normalized by 7 days after return to normoxia. However, body weight remained lower even 5 weeks after return to normoxia. We conclude that leptin is decreased during neonatal hypoxia despite no change in adiposity. Furthermore, insulin is increased probably to overcome the effects of increased counterregulatory hormones (such as corticosterone).

Key words:

Corticosterone - Body Weight - Newborn - Bone Mineral Density - Anoxia - Insulin-Like Growth Factor 1

References

• 1 Elia R, Elhoyhen A B, Bugallo G, Rio M E, Bozzini C E. Effect of acute exposure to reduced atmospheric pressures on body weight, food intake and body composition in growing rats.  Acta Physiol Pharmacol Latinoam. 1985;  35 311-318
• 2 Fushiki T, Kano T, Ito K, Hirofuji C, Inoue K, Moritani T, Sugimoto E. Effects of chronic hypoxia on the whole-body insulin action in rats.  Can J Physiol Pharmacol. 1992;  70 1522-1524
• 3 Gloster J, Hasleton P S, Harris P, Heath D. Effects of chronic hypoxia and diet on the weight and lipid content of viscera in the guinea-pig.  Environ Physiol Biochem. 1974;  4 251-258
• 4 Moromisato D Y, Moromisato M Y, Brasel J A, Cooper D M. Effect of growth hormone therapy in mitigating hypoxia-induced and food restriction-induced growth retardation in the newborn rat.  Crit Care Med. 1999;  27 2234-2238
• 5 Moromisato D Y, Moromisato M Y, Zanconato S, Roberts C T, Brasel J A, Cooper D M. Effect of hypoxia on lung, heart, and liver insulin-like growth factor-I gene and receptor expression in the newborn rat.  Crit Care Med. 1996;  24 919-924
• 6 Raff H, Bruder E D, Jankowski B M. The effect of hypoxia on plasma leptin and insulin in newborn and juvenile rats.  Endocrine. 1999;  11 37-39
• 7 Singh S B, Sharma A, Sharma K N, Selvamurthy W. Effect of high-altitude hypoxia on feeding responses and hedonic matrix in rats.  J Appl Physiol. 1996;  80 1133-1137
• 8 Tschop M, Strasburger C J, Hartmann G, Biollaz J, Bartsch P. Raised leptin concentrations at high altitude associated with loss of appetite.  Lancet. 1998;  352 1119-1120
• 9 Tschop M, Strasburger C J, Topfer M, Hautmann H, Riepl R, Fischer R, Hartmann G, Morrison K, Appenzeller M, Hildebrandt W, Biollaz J, Bartsch P. Influence of hypobaric hypoxia on leptin levels in men.  Int J Obesity. 2000;  24 S151
• 10 Cheng N, Cai W, Jiang M, Wu S. Effect of hypoxia on blood glucose, hormones, and insulin receptor functions in newborn calves.  Pediatr Res. 1997;  41 852-856
• 11 Mlekusch W, Paletta B, Truppe W, Paschke E, Grimus R. Plasma concentrations of glucose, corticosterone, glucagon and insulin and liver content of metabolic substrates and enzymes during starvation and additional hypoxia in the rat.  Horm Metab Res. 1981;  13 612-614
• 12 Sawhney R C, Malhotra A S, Singh T, Rai R M, Sinha K C. Insulin secretion at high altitude in man.  Int J BIometeor. 1986;  30 231-238
• 13 Raff H, Chadwick C J. Aldosterone responses to ACTH during hypoxia in conscious rats.  Clin Exper Pharmacol Physiol. 1986;  13 827-830
• 14 Raff H, Jankowski B M, Bruder E D, Engeland W C, Oaks M K. The effect of hypoxia from birth on the regulation of aldosterone in the 7-day-old rat: plasma hormones, steroidogenesis in vitro, and steroidogenic enzyme mRNA.  Endocrinology. 1999;  140 3147-3153
• 15 Raff H, Sandri R B, Segerson T P. Renin, ACTH, and adrenocortical function during hypoxia and hemorrhage in conscious rats.  Am J Physiol. ¿1986;  250 R240-R244
• 16 Thomas T, Marshall J M. A study on rats of the effects of chronic hypoxia from birth on respiratory and cardiovascular responses evoked by acute hypoxia.  J Physiol. 1995;  487 513-525
• 17 Fruhbeck G, Jebb S A, Prentice A M. Leptin: physiology and pathophysiology.  Clin Physiol. 1998;  5 399-419
• 18 Ahima R S, Flier J S. Leptin.  Annu Rev Physiol. 2000;  62 413-437
• 19 Ahima R S, Prabakaran D, Flier J S. Postnatal leptin surge and regulation of circadian rhythm of leptin by feeding.  J Clin Invest. 1998;  101 1020-1027
• 20 Kiess W, Siebler T, Englaro P, Kratzsch J, Deutscher J, Meyer K, Gallaher B, Blum W F. Leptin as a metabolic regulator during fetal and neonatal life and in childhood and adolescence.  J Pediatr Endocrinol Metab. 1998;  11 483-496
• 21 Kirel B, Tekin N, Tekin B, Kilic F S, Dogruel N, Aydogdu S D. Cord blood leptin levels: relationship to body weight, body mass index, sex and insulin and cortisol levels of maternal-newborn pairs at delivery.  J Pediatr Endocrinol Metab. 2000;  13 71-77
• 22 Trottier G, Koski K G, Brun T, Toufexis D J, Richard D, Walker C-D. Increased fat intake during lactation modifies hypothalamic-pituitary-adrenal responsiveness in developing rat pups: a possible role for leptin.  Endocrinology. 1998;  139 3704-3711
• 23 Raff H, Bruder E D, Jankowski B M, Goodfriend T L. Neonatal hypoxic hyperlipidemia in the rat: effects on aldosterone and corticosterone synthesis in vitro.  Am J Physiol Regulatory Integrative Comp Physiol. 2000;  278 R663-R668
• 24 Wehrenberg W B, Bergman P J, Staff L, Ndon J, Guistina A. Glucocorticoid inhibition of growth in rats: partial reversal with somatostatin antibodies.  Endocrinology. 1990;  127 2705-2708
• 25 Zhang Y-S, Du J-Z. The response of growth hormone and prolactin of rats to hypoxia.  Neurosci Lett . 2000;  279 137-140
• 26 Chen X-Q, Du J-Z. Hypoxia influences somatostatin release in rats.  Neurosci Lett. 2000;  284 151-154
• 27 Silvestrini G, Ballanti P, Patacchioli F R, Mocett I, DiGrezia R, Wedard B M, Angelucci L, Bonucci E. Evaluation of apoptosis and the glucocorticoid receptor in the cartilage growth plate and metaphyseal bone cells of rats after high-dose treatment with corticosterone.  Bone. 2000;  26 33-42