Download PDF
Horm Metab Res 2010; 42(7): 496-501
DOI: 10.1055/s-0030-1249651
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Energy Expenditure, Lipid Profile, Oxidative Stress, and Cardiac Energy Metabolism After Growth Hormone Treatment in Obese Young Rats

F. R. F. Seiva1 , C. M. S. Berbert2 , G. A. Souza1 , K. K. H. Rocha2 , G. M. X. Ebaid1 , R. C. M. Burneiko3 , E. L. B. Novelli2
  • 1Post Graduation Course, Department of Clinical and Cardiology, School of Medicine, São Paulo State University, UNESP, Botucatu, São Paulo, Brazil
  • 2Department of Chemistry and Biochemistry, Institute of Biological Sciences, São Paulo State University, UNESP, 18618-000, Botucatu, São Paulo, Brazil
  • 3Department of Physiotherapy, Faculty of Sciences and Technology, São Paulo State University, UNESP, Presidente Prudente, São Paulo, Brazil
Further Information

Publication History

received 17.10.2009

accepted 24.02.2010

Publication Date:
31 March 2010 (online)

Also available at
    Permissions and Reprints

Abstract

Obesity is rampant in modern society and growth hormone (GH) could be useful as adjunct therapy to reduce the obesity-induced cardiovascular damage. To investigate GH effects on obesity, initially 32 male Wistar rats were divided into two groups (n=16): control (C) was fed standard-chow and water and hypercaloric (H) was fed hypercaloric chow and 30% sucrose in its drinking water. After 45 days, both C and H groups were divided into two subgroups (n=8): C+PL was fed standard-chow, water and received saline subcutaneously; C+GH was fed standard-chow, water, and received 2 mg/kg/day GH subcutaneously; H+PL was fed hypercaloric diet, 30% sucrose in its drinking water, and received saline subcutaneously; and H+GH was fed hypercaloric diet, 30% sucrose in its drinking water, and received GH subcutaneously. After 75 days of total experimental period, H+PL rats were considered obese, having higher body weight, body mass index, Lee-index, and atherogenic index (AI) compared to C+PL. Obesity was accompanied by enhanced myocardial lipid hydroperoxide (LH) and lactate dehydrogenase (LDH), as well of depressed energy expenditure (RMR) and oxygen consumption(VO2)/body weight. H+GH rats had higher fasting RMR, as well as lower AI and myocardial LH than H+PL. Comparing C+GH with C+PL, despite no effects on morphometric parameters, lipid profile, myocardial LH, and LDH activity, GH enhanced fed RMR and myocardial pyruvate dehydrogenase. In conclusion, the present study brought new insights into the GH effects on obesity related cardiovascular damage demonstrating, for the first time, that GH regulated cardiac metabolic pathways, enhanced energy expenditure and improved the lipid profile in obesity condition. Growth hormone in standard fed condition also offered promising therapeutic value enhancing pyruvate-dehydrogenase activity and glucose oxidation in cardiac tissue, thus optimizing myocardial energy metabolism.

Key words

growth hormone - calorimetry - lipid profile - heart - energy metabolism - oxidative stress

References

  • 1 Hill JO. Understanding and addressing the epidemic of obesity: an energy balance perspective.  Endocr Rev. 2006;  27 750-761
    Google Scholar
  • 2 Diniz YS, Burneiko R, Seiva F, Galhardi C, Mani F, Novelli ELB. Diet compounds, glycemic index and obesity-related cardiac effects.  Int J Cardiol. 2008;  124 92-99
    Google Scholar
  • 3 Owen CG, Whincup PH, Orfei L, Chou QA, Rudnicka AR, Wathern AK, Kaye SJ, Eriksson JG, Osmond C, Cook DG. Is body mass index before middle age related to coronary heart disease risk in later life? Evidence from observational studies.  Int J Obes. 2009;  7 1-12
    Google Scholar
  • 4 Carvajal K, Hafidi M, Marin-Hernandez A, Moreno-Sanchez R. Structural and functional changes in heart mitochondria from sucrose-fed hypertriglyceridemic rats.  Biochim Biophys Acta. 2005;  1709 231-239
    Google Scholar
  • 5 Lopaschuk GD, Folmes CDL, Stanley WC. Cardiac energy metabolism in obesity.  Circ Res. 2007;  101 335-347
    Google Scholar
  • 6 Novelli ELB, Santos P, Assalin H, Souza G, Rocha K, Ebaid G, Seiva F, Mani F, Fernandes A. N-acetylcysteine in high sucrose induced obesity: energy expenditure, metabolic shifting for cardiac health.  Pharmacol Res. 2009;  59 74-79
    Google Scholar
  • 7 Yue TL, Bao W, Gu JL, Cui J, Tao L, Ma XL, Ohlstein EH, Jucker BM. Rosiglitazone treatment in Zucker diabetic fatty rats is associated with ameliorated cardiac insulin resistance and protection from ischemia reperfusion-induced myocardial injury.  Diabetes. 2005;  54 554-562
    Google Scholar
  • 8 Shadid S, Jensen MD. Effects of growth hormone administration in human obesity.  Obes Res. 2003;  11 170-175
    Google Scholar
  • 9 Mekala KC, Tritos NA. Effects of recombinant growth hormone therapy in obesity in adults: A metaanalalysis.  J Clin Endocrinol Metab. 2009;  94 130-137
    Google Scholar
  • 10 Johansen T, Laurino C, Barreca A, Malmlöf K. Reduction of adiposity with prolonged growth hormone treatment in old obese rats: effects on gluco handling and early insulin signaling.  Growth Horm IGF-I Res. 2005;  15 55-63
    Google Scholar
  • 11 Johannsson G, Mårin P, Lönn L, Ottosson M, Stenlöf K, Björntorp P, Sjöström L, Bengtsson BA. Growth hormone treatment of abdominally obese men reduces abdominal fat mass, improves glucose and lipoprotein metabolism, and reduces diastolic blood pressure.  J Clin Endocrinol Metab. 1997;  82 727-734
    Google Scholar
  • 12 Lopaschuk GD, Folmes CDL, Stanley WC. Cardiac energy metabolism in obesity.  Circ Res. 2007;  101 335-347
    Google Scholar
  • 13 Laron Z. Insulin – a growth hormone.  Arch Physiol Biochem. 2008;  114 11-16
    Google Scholar
  • 14 Wilson CR, Tran MK, Salazar KL, Young ME, Taegtmeyer H. Western diet, but not high fat diet causes derangements of fatty acid metabolism and contractile dysfunction in the heart of Wistar rats.  Biochem J. 2007;  15 457-467
    Google Scholar
  • 15 Jurdak N, Kanarek RB. Sucrose-induced obesity impairs novel object recognition learning in young rats.  Physiol Behav. 2009;  96 1-5
    Google Scholar
  • 16 Souza GA, Ebaid GX, Seiva FRF, Rocha KHR, Galhardi CM, Mani F, Novelli ELB. N-acetylcysteine in Allium plant compound improves high-sucrose diet-induced obesity and related effects.  Evid Based Complement Alternat Med. 2008;  11 1-7
    Google Scholar
  • 17 Seiva FRF, Ebaid GMX, Castro AVB, Okoshi K, Nascimento A, Rocha KKH, Padovani CR, Cicogna AC, Novelli ELB. Growth Hormone and heart failure: oxidative stress and energetic metabolism in rats.  Growth Horm IGF-I Res. 2008;  18 275-283
    Google Scholar
  • 18 Pérez-Romero A, Amores A, Salamé F, Ariznavarreta C, Tresguerrez JÁ. Efectos de la administración de rhGH en ratas macho viejas.  Endocrinol Nutr. 1999;  46 31
    Google Scholar
  • 19 Castillo C, Cruzado M, Ariznavarreta C, Gil-Loyzaga P, Lahera V, Cachofeiro V, Tresguerres JA. Effect of recombinant human growth hormone on body composition and vascular function and structure in old male Wistar rats.  Biogerontology. 2005;  6 303-312
    Google Scholar
  • 20 Novelli ELB, Diniz YS, Galhardi C, Ebaid G, Rodrigues H, Mani F. Anthropometrical parameters and markers of obesity in rats.  Lab Anim. 2007;  41 111-119
    Google Scholar
  • 21 Labayen I, Forga L, Martinez JA. Nutrient oxidation and metabolic rate as affected by meals containing different proportions of carbohydrate and fat, in healthy young women.  Eur J Nutr. 1999;  38 158-166
    Google Scholar
  • 22 Castelli WP, Abbot RD, Mcnamara PM. Summary estimates of cholesterol used to predict coronary heart disease.  Circ. 1983;  67 730-734
    Google Scholar
  • 23 Lowry OH, Rosembrough NL, Farr AL, Randall RJ. Protein measurement with the folin-phenol reagent.  J Biol Chem. 1951;  193 265-275
    Google Scholar
  • 24 Jiang ZY, Woollard A, Wolff S. Lipid hydroperoxide measurement by oxidation of Fe3+ in the presence of xylenol orange.  Lipids. 1991;  26 853-856
    Google Scholar
  • 25 Bass A, Brdicka PE, Eyer P, Hofer S, Pette D. Metabolic differentiation of distinct muscle types at the level of enzymatic organization.  Eur J Biochem. 1969;  10 198-206
    Google Scholar
  • 26 Rasmussen MH. Obesity, growth hormone and weight loss.  Mol Cell Endocrinol. 2010;  316 147-153
    Google Scholar
  • 27 Bieri JG, Stoenband GS, Briggs GM, Phillips RW, Woodand JC, Knpha JJ. American Institute of Nutrition. Report of the American Institute of nutrition Ad Hoc Committee on Standards for nutritional studies.  J Nutr. 1977;  107 1340-1348
    Google Scholar
  • 28 Malmlöf K, Din N, Johansen T, Pedersen S. Growth hormone affects both adiposity and voluntary food intake in old and obese female rats.  Eur J Endocrinol. 2002;  146 121-128
    Google Scholar
  • 29 Roberts TJ, Azain MT. Effect of somatotropin on rate and composition of gain and feed intake in young pituitary intact female rats.  Growth Dev Aging. 1995;  59 3-13
    Google Scholar
  • 30 Stortelien LH, Kraegen EW, Jenkins AB. Effects of sucrose vs. starch diets on in vivo insulin action thermogenesis and obesity in rats.  Am J Clin Nutr. 1988;  47 420-427
    Google Scholar
  • 31 Brizzi P, Tonolo G, Carusillo F, Malaguarnera M, Maioli, Musumeci S. Plasma lipid composition and LDL oxidation.  Clin Chem Lab Med. 2003;  4 56-60
    Google Scholar
  • 32 Rudling M, Norstedt G, Olivecrona H, Reihnér E, Gustafsson J, Angelin B. Importance of growth hormone for the induction of hepatic low density lipoprotein receptors.  Proc Natl Acad Sci USA. 1992;  89 6983-6987
    Google Scholar
  • 33 Hjalmarson A, Isaksson O, Ahrén K. Effects of growth hormone and insulin on amino acid transport in perfused rat heart.  Am J Physiol. 1969;  217 1795-1802
    Google Scholar
  • 34 Niki E, Yoshida Y, Saito Y, Noguchi N. Lipid peroxidation: mechanisms, inhibition and biological effects.  Biochem Biophys Res Commun. 2005;  338 668-676
    Google Scholar
  • 35 Kaasik A, Veksler V, Boehm E, Novotova M, Minajeva A, Ventura-Clapier R. Energetic crosswalk between organelles: architectural integration of energy production and utilization.  Circ Res. 2001;  89 153-159
    Google Scholar

Correspondence

E. L. B. Novelli

Department of Chemistry and Biochemistry

Institute of Biological Sciences

São Paulo State University

UNESP

18618-000 Botucatu

São Paulo, Brazil

Phone: +55/14/3811 6255

Fax: +55/14/3815 3744

Email: drno@uol.com.br