RSS-Feed abonnieren
DOI: 10.1055/s-0031-1273769
© Georg Thieme Verlag KG Stuttgart · New York
Calorimetry, Morphometry, Oxidative Stress, and Cardiac Metabolic Response to Growth Hormone Treatment in Obese and Aged Rats
Publikationsverlauf
received 08.11.2010
accepted 23.02.2011
Publikationsdatum:
29. März 2011 (online)

Abstract
This study investigated the effects of growth hormone therapy on energy expenditure, lipid profile, oxidative stress and cardiac energy metabolism in aging and obesity conditions. Life expectancy is increasing in world population and with it, the incidence of public health problems such as obesity and cardiac alterations. Because growth hormone (GH) concentration is referred to be decreased in aging conditions, a question must be addressed: what is the effect of GH on aging related adverse changes? To investigate the effects of GH on cardiac energy metabolism and its association with calorimetric parameters, lipid profile and oxidative stress in aged and obese rats, initially 32 male Wistar rats were divided into 2 groups (n=16), C: given standard-chow and water; H: given hypercaloric-chow and receiving 30% sucrose in its drinking water. After 45 days, both C and H groups were divided into 2 subgroups (n=8), C+PL: standard-chow, water, and receiving saline subcutaneously; C+GH: standard-chow, water, and receiving 2 mg/kg/day rhGH subcutaneously; H+PL: hypercaloric-chow, 30% sucrose, receiving saline subcutaneously; H+GH: hypercaloric-chow, 30% sucrose, receiving rhGH subcutaneously. After 30 days, C+GH and H+PL rats had higher body mass index, Lee-index, body fat content, percent-adiposity, serum triacylglycerol, cardiac lipid-hydroperoxide, and triacylglycerol than C+PL. Energy-expenditure (RMR)/body weight, oxygen consumption and fat-oxidation were higher in H+GH than in H+PL. LDL-cholesterol was highest in H+GH rats, whereas cardiac pyruvate-dehydrogenase and phosphofrutokinase were higher in H+GH and H+PL rats than in C+PL. In conclusion, the present study brought new insights on aging and obesity, demonstrating for the first time that GH therapy was harmful in aged and obesity conditions, impairing calorimetric parameters and lipid profile. GH was disadvantageous in control old rats, having undesirable effects on triacylglycerol accumulation and cardiac oxidative stress.
Key words
growth hormone - obesity - aging - cardiac energy metabolism
References
- 1
Kireev RA, Tresguerres ACF, Castillo C, Salazar V, Ariznavarreta C, Vara E, Tresguerres JAF.
Effect of exogenous administration of melatonin and growth hormone on pro-oxidant
functions of the liver in aging male rats.
J Pineal Res.
2007;
42
64-70
Reference Ris Wihthout Link
- 2
Everitt AV, Cavanagh LM.
The ageing process in the hypophysectomized rat.
Gerontologia.
1965;
11
198-207
Reference Ris Wihthout Link
- 3
Brown-Borg HM.
Hormonal regulation of longevity in mammals.
Ageing Res Rev.
2007;
6
28-45
Reference Ris Wihthout Link
- 4
Copeland KC, Colleti BR, Devlin JT, McAuliffe TL.
The relationship between insulin-like growth factor-I, adiposity and aging.
Metabolism.
1990;
39
584-587
Reference Ris Wihthout Link
- 5
Hajima SV, Van Dam PS, Vries WR, Maitimu-Smeele I, Dieguez C, Casanueva FF, Koppeschaar HP.
The GHRH/GHRP-6 test for diagnosis of GH deficiency in elderly or severely obese men.
Eur J Endocrinol.
2005;
152
575-580
Reference Ris Wihthout Link
- 6
Shadid S, Jensen MD.
Effects of growth hormone administration in human obesity.
Obes Res.
2003;
11
170-175
Reference Ris Wihthout Link
- 7
Despres JP, Lemieux I, Prud’homme D.
Treatment of obesity: need to focus on high risk abdominally obese patients.
Br Med J.
2001;
322
716-720
Reference Ris Wihthout Link
- 8
Cuttica CM, Castoldi L, Gorrini GP, Peluffo F, Delitala G, Filippa P, Fanciulli G, Giusti M.
Effects of six-month administration of rhGH to healthy elderly subjects.
Aging.
1997;
9
193-197
Reference Ris Wihthout Link
- 9
Angelopoulos TJ, Seip RL, Cole TG.
Effect of short-term recombinant hGH administration on plasma lipoprotein in elderly
adults.
Gerontology.
1998;
44
228-231
Reference Ris Wihthout Link
- 10
Hill JO.
Understanding and addressing the epidemic of obesity: an energy balance perspective.
Endocr Rev.
2006;
27
750-761
Reference Ris Wihthout Link
- 11
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
Reference Ris Wihthout Link
- 12
Rosén T, Bengtsson BA.
Premature mortality due to cardiovascular disease in hypopituitarism.
Lancet.
1990;
336
285-288
Reference Ris Wihthout Link
- 13
Novelli ELB, Souza GA, Ebaid GMX, Rocha KKHR, Seiva FRF, Mani F, Campos KE, Sforcin JM.
Energy expenditure and oxygen consumption as novel biomarkers of obesity-induced cardiac
disease in rats.
Obesity.
2010;
18
1754-1761
Reference Ris Wihthout Link
- 14
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
Reference Ris Wihthout Link
- 15
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
Reference Ris Wihthout Link
- 16
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
Reference Ris Wihthout Link
- 17
Seiva FRF, Berbert CMS, Souza GA, Rocha KKH, Ebaid GMX, Burneiko RCM, Novelli ELB.
Energy expenditure, lipid profile, oxidative stress and cardiac energy metabolism
after growth hormone treatment in obese young rats.
Horm Metab Res.
2010;
42
486-501
Reference Ris Wihthout Link
- 18
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
Reference Ris Wihthout Link
- 19
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
Reference Ris Wihthout Link
- 20
Nascimento AF, Sugizaki MM, Leopoldo AS, Lima-Leopoldo AP, Nogueira CR, Novelli ELB, Padovani CR, Cicogna AC.
Misclassification probability as obese or lean in hypercaloric and normocaloric diet.
Biol Res.
2008;
41
253-259
Reference Ris Wihthout Link
- 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
Reference Ris Wihthout Link
- 22
Diniz YS, Burneiko RM, Seiva FRF, Almeida FQA, Galhardi CM, Novelli Filho JLVB, Mani F, Novelli ELB.
Diet compounds, glycemic index and obesity-related cardiac effects.
Int J Cardiol.
2008;
124
92-99
Reference Ris Wihthout Link
- 23
Castelli WP, Abbot RD, Mcnamara PM.
Summary estimates of cholesterol used to predict coronary heart disease.
Circ.
1983;
67
730-734
Reference Ris Wihthout Link
- 24
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ.
Protein measurement with the folin-phenol reagent.
J Biol Chem.
1951;
193
265-275
Reference Ris Wihthout Link
- 25
Jiang ZY, Woollard A, Wolff S.
Lipid hydroperoxide measurement by oxidation of Fe 3+ in the presence of xylenol orange.
Lipids.
1991;
26
853-856
Reference Ris Wihthout Link
- 26
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
Reference Ris Wihthout Link
- 27
Iossa S, Lionetti L, Mollica MP, Barletta A, Liverini G.
Energy intake and utilization vary during development in rats.
J Nutr.
1999;
129
1593-1596
Reference Ris Wihthout Link
- 28
Micmacher E, Assumpção RP, Redorat RG, Spina LD, Cruz IC, Silva CA, Vaisman M, Conceição FL.
Growth hormone secretion in response to glucagon stimulation test in healthy middle-aged
men.
Arq Bras Endocrinol Metabol.
2009;
53
853-858
Reference Ris Wihthout Link
- 29
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
Reference Ris Wihthout Link
- 30
Schmidt W, Poll-Jordan G, Loffler G.
Adipose conversion of 3T3-L1 cells in a serum-free culture system depends on epidermal
growth factor, insulin-like growth factor I, corticosterone, and cyclic AMP.
J Biol Chem.
1990;
265
15489-15495
Reference Ris Wihthout Link
- 31
Chen NX, Hausman GJ, Wright JT.
Influence of thyroxine in vivo on preadipocyte development and insulin-like growth
factor-I and IGF binding protein secretion in fetal stromalvascular cell cultures.
Obes Res.
1996;
4
357-366
Reference Ris Wihthout Link
- 32
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
Reference Ris Wihthout Link
- 33
Diniz YS, Santos PP, Assalin HB, Souza GA, Rocha KK, Ebaid GM, Seiva FR, Amauchi JF, Novelli Filho JL, Novelli EL.
Conjugated Linoleic acid and cardiac health: oxidative stress and energetic metabolism
in standard and sucrose-rich diets.
Eur J Pharmacol.
2008;
579
318-325
Reference Ris Wihthout Link
- 34
Bramnert M, Segerlantz M, Laurila E, Daugaard JR, Manhem P, Groop L.
Growth hormone replacement therapy induces insulin resistance by activating the glucose-fatty
acid cycle.
J Clin Endocrinol Metab.
2003;
88
1455-1463
Reference Ris Wihthout Link
- 35
Angelin B, Rudling M.
Growth hormone and hepatic lipoprotein metabolism.
Curr Opin Lipidol.
1994;
5
160-165
Reference Ris Wihthout Link
- 36
Elam MB, Wilcox HG, Solomon SS, Heimberg M.
In vivo growth hormone treatment stimulates secretion of very low density lipoprotein
by the isolated perfused rat liver.
Endocrinology.
1992;
131
2717-2722
Reference Ris Wihthout Link
- 37
Sjoberg A, Oscarsson J, Eden S, Olofsson SO.
Continuous but not intermittent administration of growth hormone to hypophysectomized
rats increases apolipoprotein-E secretion from cultured hepatocytes.
Endocrinology.
1994;
134
790-798
Reference Ris Wihthout Link
- 38
Rudling M, Olivecrona H, Eggertsen G, Angelin B.
Regulation of rat liver low density lipoprotein receptors: in vivo stimulation by
growth hormone is not mediated by insulin-like growth factor I.
J Clin Invest.
1996;
97
292-299
Reference Ris Wihthout Link
- 39
Rollo CD, Carlson J, Sawada M.
Accelerated aging of giant transgenic mice is associated with elevated free radical
process.
Can J Zool.
1996;
74
606-620
Reference Ris Wihthout Link
- 40
Bartke A, Brown-Borg H.
Life extension in the dwarf mouse.
Curr Top Dev Biol.
2004;
63
189-225
Reference Ris Wihthout Link
- 41
Lopaschuk GD, Folmes CDL, Stanley WC.
Cardiac energy metabolism in obesity.
Circ Res.
2007;
101
335-347
Reference Ris Wihthout Link
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
Telefon: +55/14/381 162 55
Fax: +55/14/381 537 44
eMail: drno@uol.com.br