Download PDF
Horm Metab Res 2003; 35(4): 243-250
DOI: 10.1055/s-2003-39481
Original Clinical
© Georg Thieme Verlag Stuttgart · New York

Growth Hormone-Mediated Breakdown of Body Fat: Effects of GH on Lipases in Adipose Tissue and Skeletal Muscle of Old Rats Fed Different Diets

T.  Johansen 1, 3 , B.  Richelsen 2 , H.  S.  Hansen 3 , N.  Din 4 , K.  Malmlöf 1
  • 1 Dept. of Pharmacology 3, Novo Nordisk, Malov, Denmark
  • 2 Aarhus County Hospital, Aarhus, Denmark
  • 3 The Royal Danish School of Pharmacy, Dept. of Pharmacology, Copenhagen, Denmark
  • 4 Novo Nordisk, Dept. of Transcription Biology, Bagsvaerd, Denmark.
Further Information

Publication History

Received 4 October 2002

Accepted after Revision 9 December 2002

Publication Date:
02 June 2003 (online)

Also available at
    Permissions and Reprints

Abstract

Lipid storage and breakdown is mainly controlled by lipoprotein lipase and hormone-sensitive lipase. The aim of this work was to elucidate whether growth hormone mediated loss of adipose tissue involves a concerted action on tissue lipases, and to what degree such events are modulated by dietary regimen. Twelve-month-old rats fed first a high-fat diet or a low-fat diet for 14 weeks were injected with saline or growth hormone (4 mg/kg/d) for four days or three weeks in different combinations with either high- or low-fat diets. In adipose tissue, growth hormone generally inhibited lipoprotein lipase and also attenuated the inhibiting effect of insulin on hormone-sensitive lipase activity. Growth hormone treatment combined with restricted high-fat feeding reduced the activity of both lipases in adipose tissue and stimulated hormone-sensitive lipase in muscle. Generally, plasma levels of free fatty acids, glycerol and cholesterol were reduced by growth hormone, and in combination with restricted high-fat feeding, triglyceride levels improved too. We conclude that growth hormone inhibits lipid storage in adipose tissue by reducing both lipoprotein lipase activity and insulin's inhibitory action on hormone-sensitive lipase. We also propose that growth hormone's effects on tissue lipases and blood lipids are modulated by dietary regimen.

Key words

Adipose tissue - High-fat diet - Obesity - Hormone-sensitive lipase - Lipoprotein lipase - Blood lipids - Gene expression

References

  • 1 Johannsson G, Marin P, Lonn L, Ottosson M, Stenlof K, Bjorntorp P, Sjostrom L, Bengtsson B A. 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
    CrossrefPubMedGoogle Scholar
  • 2 Richelsen B, Pedersen S B, Borglum J D, Moller-Pedersen T, Jorgensen J, Jorgensen J O. Growth hormone treatment of obese women for 5 wk: effect on body composition and adipose tissue LPL activity.  Am J Physiol. 1994;  266 E211-E216
    PubMedGoogle Scholar
  • 3 Kamel A, Norgren S, Elimam A, Danielsson P, Marcus C. Effects of growth hormone treatment in obese prepubertal boys.  J Clin Endocrinol Metab. 2000;  85 1412-1419
    CrossrefPubMedGoogle Scholar
  • 4 Skaggs S R, Crist D M. Exogenous human growth hormone reduces body fat in obese women.  Horm Res. 1991;  35 19-24
    PubMedGoogle Scholar
  • 5 Münzer T, Harman S M, Hees P, Shapiro E, Christmas C, Bellantoni M F, Stevens T E, O'Connor K G, Pabst K M, St C lair, Sorkin J D, Blackman M R. Effects of GH and/or sex steroid administration on abdominal subcutaneous and visceral fat in healthy aged women and men.  J Clin Endocrinol Metab. 2001;  86 3604-3610
    CrossrefPubMedGoogle Scholar
  • 6 Fryberg D A, Gelfand R A, Barret E J. Growth Hormone Acutely stimulates forearm muscle protein synthesis in normal humans.  Am J Physiol. 1991;  260 E499-E504
    PubMedGoogle Scholar
  • 7 Haymond M W, Horber F F, de Feo P, Kahn S E, Mauras N. Effect of human growth hormone and insulin-like growth factor I on whole- body leucine and estimates of protein metabolism.  Horm Res. 1993;  40 92-94
    PubMedGoogle Scholar
  • 8 Crowley V EF, Yeo S HG, O'Rahilley S. Obesity therapy: altering the energy intake-and-expenditure balance sheet.  Nature Reviews. 2002;  1 276-286
    PubMedGoogle Scholar
  • 9 Ng F M, Sun J, Sharma L, Libinaka R, Jiang W J, Gianello R. Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone.  Horm Res. 2000;  53 274-278
    CrossrefPubMedGoogle Scholar
  • 10 Auwerx J, Leroy P, Schoonjans K. Lipoprotein Lipase: Recent contributions from molecular biology.  Crit Rev Clin Lab Sci. 1992;  29 243-268
    PubMedGoogle Scholar
  • 11 Zechner R. The Tissue-Specific Expression of lipoprotein lipase: implications for energy and lipoprotein metabolism.  Curr Opin Lipidol. 1997;  8 77-88
    PubMedGoogle Scholar
  • 12 Holm C, Kirchgessner T G, Svenson K L, Fredrikson G, Nilsson S, Miller C G, Shively J E, Heinzmann C, Sparkes R S, Mohandas T. et al . Hormone-sensitive lipase: sequence, expression, and chromosomal localization to 19 Cent-Q13.3.  Science. 1988;  241 1503-1506
    PubMedGoogle Scholar
  • 13 Holm C, Osterlund T, Laurell H, Contreras J A. Molecular Mechanisms Regulating hormone-sensitive lipase and lipolysis.  Annu Rev Nutr. 2000;  20 365-393
    CrossrefPubMedGoogle Scholar
  • 14 Langin D, Lucas S, Lafontan M. Millennium fat-cell lipolysis reveals unsuspected novel tracks.  Horm Metab Res. 2000;  32 443-452
    PubMedGoogle Scholar
  • 15 Coppack S W, Evans R D, Fisher R M, Frayn K N, Gibbons G F, Humphreys S M, Kirk M L, Potts J L, Hockaday T D. Adipose tissue metabolism in obesity: lipase action in vivo before and after a mixed meal.  Metab Clin Exp. 1992;  41 264-272
    CrossrefPubMedGoogle Scholar
  • 16 Frayn K N, Coppack S W, Fielding B A, Humphreys S M. Coordinated regulation of hormone-sensitive lipase and lipoprotein lipase in human adipose tissue in vivo: implications for the control of fat storage and fat mobilization.  Adv Enzyme Regul. 1995;  35 163-178
    PubMedGoogle Scholar
  • 17 Sztalryd C, Kraemer F B. Regulation of hormone-sensitive lipase during fasting.  Am J Physiol. 1994;  266 E179-E185
    PubMedGoogle Scholar
  • 18 Bergo M, Wu G S, Ruge T, Olivecrona T. Down-regulation of adipose tissue lipoprotein lipase during fasting requires that a gene, separate from the lipase gene, is switched on.  J Biol Chem. 2002;  277 11 927-11 932
    PubMedGoogle Scholar
  • 19 Ottosson M, Vikman-Adolfsson K, Enerback S, Elander A, Bjorntorp P, Eden S. Growth hormone inhibits lipoprotein lipase activity in human adipose tissue.  J Clin Endocrinol Metab. 1995;  80 936-941
    CrossrefPubMedGoogle Scholar
  • 20 Oscarsson J, Ottosson M, Eden S. Effects of growth hormone on lipoprotein lipase and hepatic lipase.  J Edocrinol Invest. 1999;  22 2-9
    PubMedGoogle Scholar
  • 21 Murase T, Yamada N, Matsuzaki F. The in vitro effect of growth hormone on adipose tissue lipoprotein lipase in rats.  Life Sci. 1981;  28 199-201
    CrossrefPubMedGoogle Scholar
  • 22 Slavin B G, Ong J M, Kern P A. Hormonal regulation of hormone-sensitive lipase activity and MRNA levels in isolated rat adipocytes.  J Lipid Res. 1994;  35 1535-1541
    PubMedGoogle Scholar
  • 23 Fain J N, Bahouth S W. Regulation of lipolysis and leptin biosynthesis in rodent adipose tissue by growth hormone.  Metab Clin Exp. 2000;  49 239-244
    PubMedGoogle Scholar
  • 24 Dietz J, Schwartz J. Growth hormone alters lipolysis and hormone-sensitive lipase activity in 3T3-F442A adipocytes.  Metab Clin Exp. 1991;  40 800-806
    PubMedGoogle Scholar
  • 25 Vahl N, Moller N, Lauritzen T, Christiansen J S, Jorgensen J O. Metabolic effects and pharmacokinetics of a growth hormone pulse in healthy adults: relation to age, sex, and body composition.  J Clin Endocrinol Metab. 1997;  82 3612-3618
    CrossrefPubMedGoogle Scholar
  • 26 Richelsen B, Pedersen S B, Kristensen K, Borglum J D, Norrelund H, Christiansen J S, Jorgensen J O. Regulation of lipoprotein lipase and hormone-sensitive lipase activity and gene expression in adipose and muscle tissue by growth hormone treatment during weight loss in obese patients.  Metab Clin Exp. 2000;  49 906-911
    PubMedGoogle Scholar
  • 27 Reynisdottir S, Dauzats M, Thorne A, Langin D. Comparison of hormone-sensitive lipase activity in visceral and subcutaneous human adipose tissue.  J Clin Endocrinol Metab. 1997;  82 4162-4166
    CrossrefPubMedGoogle Scholar
  • 28 Hietanen E, Greenwood M R. A comparison of lipoprotein lipase activity and adipocyte differentiation in growing male rats.  J Lipid Res. 1977;  18 480-490
    PubMedGoogle Scholar
  • 29 Richelsen B, Pedersen S B, Moller-Pedersen T, Schmitz O, Moller N, Borglum J D. Lipoprotein lipase activity in muscle tissue influenced by fatness, fat distribution and insulin in obese females.  Eur J Clin Invest. 1993;  23 226-233
    PubMedGoogle Scholar
  • 30 Lithell H, Boberg J. Determination of lipoprotein-lipase activity in human skeletal muscle tissue.  Biochim Biophys Acta. 1978;  528 58-68
    PubMedGoogle Scholar
  • 31 Malmlof K, Din N, Johansen T, Pedersen S B. Growth hormone affects both adiposity and voluntary food intake in old and obese female Rats.  Eur J Endocrinol. 2002;  146 121-128
    CrossrefPubMedGoogle Scholar
  • 32 Stich V, Harant I, de Glisezinski I, Crampes F, Berlan M, Kunesova M, Hainer V, Dauzats M, Riviere D, Garrigues M, Holm C, Lafontan M, Langin D. Adipose tissue lipolysis and hormone-sensitive lipase expression during very-low-calorie diet in obese female identical twins.  J Clin Endocrinol Metab. 1997;  82 739-744
    CrossrefPubMedGoogle Scholar
  • 33 Sadur C N, Eckel R H. Insulin stimulation of adipose tissue lipoprotein lipase. use of the euglycemic clamp technique.  J Clin Invest. 1982;  69 1119-1125
    PubMedGoogle Scholar
  • 34 Hickner R C, Racette S B, Binder E F, Fisher J S, Kohrt W M. Suppression of whole body and regional lipolysis by insulin: effects of obesity and exercise.  J Clin Endocrinol Metab. 1999;  84 3886-3895
    CrossrefPubMedGoogle Scholar
  • 35 Botion L M, Green A. Long-Term regulation of lipolysis and hormone-sensitive lipase by insulin and glucose.  Diabetes. 1999;  48 1691-1697
    PubMedGoogle Scholar
  • 36 Kolehmainen M, Vidal H, Ohisalo J J, Pirinen E, Alhava E, Uusitupa M I. Hormone-sensitive lipase expression and adipose tissue metabolism show gender difference in obese subjects after weight loss.  Int J Obes. 2002;  26 6-16
    CrossrefPubMedGoogle Scholar
  • 37 Hettiarachchi M, Watkinson A, Jenkins A B, Theos V, Ho K K, Kraegen E W. Growth hormone-induced insulin resistance and its relationship to lipid availability in the rat.  Diabetes. 1996;  45 415-421
    PubMedGoogle Scholar
  • 38 Aloia J F, Zanzi I, Cohn S H. Absence of an effect of chronic administration of growth hormone on serum lipids.  Metab Clin Exp. 1975;  24 795-798
    PubMedGoogle Scholar
  • 39 Jorgensen J O, Pedersen S B, Borglum J, Moller N, Schmitz O, Christiansen J S, Richelsen B. Fuel metabolism, energy expenditure, and thyroid function in growth hormone-treated obese women: a double-blind placebo-controlled study.  Metabolism. 1994;  43 872-877
    CrossrefPubMedGoogle Scholar
  • 40 Møller N, Møller J, Jørgensen J O, Ovesen P, Schmitz O, Alberti K G, Christiansen J S. Impact of 2 weeks high dose growth hormone treatment on basal and insulin stimulated substrate metabolism in humans.  Clin Endocrinol (Oxf). 1993;  39 577-581
    CrossrefPubMedGoogle Scholar
  • 41 Nikkila E A, Pelkonen R. Serum lipids in acromegaly.  Metab Clin Exp. 1975;  24 829-838
    PubMedGoogle Scholar
  • 42 Matsuo T, Suzuki M. Beef tallow diet decreases lipoprotein lipase activities in brown adipose tissue, heart, and soleus muscle by reducing sympathetic activities in rats.  J Nutr Sci Vitaminol (Tokyo). 1994;  40 569-581
    PubMedGoogle Scholar
  • 43 Kusunoki M, Hara T, Tsutsumi K, Nakamura T, Miyata T, Sakakibara F, Sakamoto S, Ogawa H, Nakaya Y, Storlien L H. The lipoprotein lipase activator, NO-1886, suppresses fat accumulation and insulin resistance in rats fed a high-fat diet.  Diabetolog. 2000;  43 875-880
    PubMedGoogle Scholar
  • 44 Roberts C K, Barnard R J, Liang K H, Vaziri N D. Effect of diet on adipose tissue and skeletal muscle VLDL receptor and LPL: implications for obesity and hyperlipidemia.  Atherosclerosis. 2002;  161 133-141
    CrossrefPubMedGoogle Scholar
  • 45 Ranganath L R, Beety J M, Wright J, Morgan L M. Nutrient regulation of post-heparin lipoprotein lipase activity in obese subjects.  Horm Metab Res. 2001;  33 57-61
    Article in Thieme ConnectPubMedGoogle Scholar
  • 46 Vessby B, Selinus I, Lithell H. Serum lipoprotein and lipoprotein lipase in overweight, type II diabetics during and after supplemented fasting.  Arteriosclerosis. 1985;  5 93-100
    PubMedGoogle Scholar
  • 47 Brehm B, Seeley R J, Daniels S R, D'Alessio D A. Comparison of a very low-carbohydrate diet and a calorie-restricted low-fat diet on body weight and cardiovascular risk factors.  Int J Obes. 2002;  26 S24
    CrossrefPubMedGoogle Scholar
  • 48 Okuda Y, Pena J, Chou J, Field J B. Effect of growth hormone on hepatic glucose and insulin metabolism after oral glucose in conscious dogs.  Am J Physiol. 1994;  267 E454-E460
    PubMedGoogle Scholar
  • 49 Nielsen S, Moller N, Christiansen J S, Jorgensen J O. Pharmacological antilipolysis restores insulin sensitivity during growth hormone exposure.  Diabetes. 2001;  50 2301-2308
    CrossrefPubMedGoogle Scholar

T. Johansen

Novo Nordisk A/S

· Novo Alle · DK-2880 Bagsvaerd · Denmark ·

Phone: +45 (44) 42 96 64/+45 (30) 79 96 64

Fax: +45 (44) 42 19 40

Email: thuj@novonordisk.com