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

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.

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
• 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
• 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
• 4 Skaggs S R, Crist D M. Exogenous human growth hormone reduces body fat in obese women.  Horm Res. 1991;  35 19-24
• 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
• 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
• 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
• 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
• 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
• 10 Auwerx J, Leroy P, Schoonjans K. Lipoprotein Lipase: Recent contributions from molecular biology.  Crit Rev Clin Lab Sci. 1992;  29 243-268
• 11 Zechner R. The Tissue-Specific Expression of lipoprotein lipase: implications for energy and lipoprotein metabolism.  Curr Opin Lipidol. 1997;  8 77-88
• 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
• 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
• 14 Langin D, Lucas S, Lafontan M. Millennium fat-cell lipolysis reveals unsuspected novel tracks.  Horm Metab Res. 2000;  32 443-452
• 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
• 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
• 17 Sztalryd C, Kraemer F B. Regulation of hormone-sensitive lipase during fasting.  Am J Physiol. 1994;  266 E179-E185
• 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
• 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
• 20 Oscarsson J, Ottosson M, Eden S. Effects of growth hormone on lipoprotein lipase and hepatic lipase.  J Edocrinol Invest. 1999;  22 2-9
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 30 Lithell H, Boberg J. Determination of lipoprotein-lipase activity in human skeletal muscle tissue.  Biochim Biophys Acta. 1978;  528 58-68
• 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
• 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
• 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
• 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
• 35 Botion L M, Green A. Long-Term regulation of lipolysis and hormone-sensitive lipase by insulin and glucose.  Diabetes. 1999;  48 1691-1697
• 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
• 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
• 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
• 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
• 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
• 41 Nikkila E A, Pelkonen R. Serum lipids in acromegaly.  Metab Clin Exp. 1975;  24 829-838
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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