Abstract
This work was performed to elucidate whether growth hormone (GH)-mediated loss of
adipose tissue and responses in plasma insulin and leptin are modulated by diet composition.
12-month-old rats were first fed a high-fat (HF) diet or a low-fat (LF) diet for 14
weeks. After that, GH or saline was administered to rat groups that were maintained
on either HF or LF diets or that were switched from the HF to the LF diet. All 6 groups
had free access to food. One additional saline group was pair-fed with the GH group
that was switched from the HF to the LF diet. The caloric consumption of this latter
group was also translated to yet another GH group receiving restricted amounts of
the HF diet. GH was given in a total dose of 4 mg/kg/d for three weeks. After sacrifice,
blood was collected and tissues were excised. In groups injected with saline, the
weight of excised adipose tissue was 60 ± 4.7, 41 ± 3.8 and 50 ± 4.5 g in animals
that continued with the HF diet, LF diet, or that were switched from HF to LF, respectively.
Corresponding figures after GH treatment were significantly (p < 0.05) decreased to
38 ± 2.7, 30 ± 2.3, and 31 ± 2.7 g, respectively. Pair-feeding had no effect, whereas
only 26 ± 3.0 g of adipose tissue was retrieved in rats fed restricted amounts of
HF diet while receiving GH. In this group, plasma insulin and leptin were also significantly
(p < 0.05) depressed compared with other GH groups, especially to the group fed the
unrestricted HF diet (203 ± 35 vs. 1345 ± 160 pmol/l and 9.3 ± 1.2 vs. 31 ± 4.4 µg/l). In conclusion, this study shows that GH mediates breakdown of adipose
tissue under a variety of dietary conditions, and that induction of hyperinsulinemia
can be prevented if GH treatment is combined with restricted feeding of a diet which
is relatively low in carbohydrates and rich in fat. This will also promote a fall
of plasma leptin.
Key words
Adipose-tissue - Body composition - High-fat diet - Muscle - Obesity - Lipolysis
References
- 1
Clapham J C, Arch J R, Tadayyon M.
Anti-obesity drugs: a critical review of current therapies and future opportunities.
Pharmacol Ther.
2001;
89
81-121
- 2
Skaggs S R, Crist D M.
Exogenous human growth hormone reduces body fat in obese women.
Horm Res.
1991;
35
19-24
- 3
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
- 4
Snyder D K, Underwood L E, Clemmons D R.
Persistent lipolytic effect of exogenous growth hormone during caloric restriction.
Am J Med.
1995;
98
129-134
- 5
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 [see comments].
J Clin Endocrinol Metab.
1997;
82
727-734
- 6
Cuneo R C, Judd S, Wallace J D, Perry-Keene D, Burger H, Lim-Tio S, Strauss B, Stockigt J,
Topliss D, Alford F, Hew L, Bode H, Conway A, Handelsman D, Dunn S, Boyages S, Cheung N W,
Hurley D.
The Australian Multicenter Trial of Growth Hormone (GH) Treatment in GH- Deficient
Adults.
J Clin Endocrinol Metab.
1998;
83
107-116
- 7
Kim K R, Nam S Y, Song Y D, Lim S K, Lee H C, Huh K B.
Low-dose growth hormone treatment with diet restriction accelerates body fat loss,
exerts anabolic effect and improves growth hormone secretory dysfunction in obese
adults.
Horm Res.
1999;
51
78-84
- 8
Isley W L, Underwood L E, Clemmons D R.
Dietary components that regulate serumsomatomedin-C concentrations in humans.
J Clin Invest.
1983;
71
175-182
- 9
Snyder D K, Clemmons D R, Underwood L E.
Dietary carbohydrate content determines responsiveness to growth hormone in energy-restricted
humans.
J Clin Endocrinol Metab.
1989;
69
745-752
- 10
Sanchez-Gomez M, Malmlof K, Mejia W, Bermudez A, Ochoa M T, Carrasco-Rodriguez S,
Skottner A.
Insulin-like growth factor-I, but not growth hormone, is dependent on a high protein
intake to increase nitrogen balance in the rat.
Br J Nutr.
1999;
81
145-152
- 11
Snyder D K, Underwood L E, Clemmons D R.
Anabolic effects of growth hormone in obese diet-restricted subjects are dose dependent.
Am J Clin Nutr.
1990;
52
431-437
- 12
Drent M L, Wever L D, Ader H J, van der Veen E A.
Growth hormone administration in addition to a very low calorie diet and an exercise
program in obese subjects.
Eur J Endocrinol.
1995;
132
565-572
- 13
Tagliaferri M, Scacchi M, Pincelli A I, Berselli M E, Silvestri P, Montesano A, Ortolani S,
Dubini A, Cavagnini F.
Metabolic effects of biosynthetic growth hormone treatment in severely energy-restricted
obese women.
Int J Obes Relat Metab Disord.
1998;
22
836-841
- 14
Nam S Y, Kim K R, Cha B S, Song Y D, Lim S K, Lee H C, Huh K B.
Low-dose growth hormone treatment combined with diet restriction decreases insulin
resistance by reducing visceral fat and increasing muscle mass in obese type 2 diabetic
patients.
Int J Obes Relat Metab Disord.
2001;
25
1101-1107
- 15
Mendel V E.
Influence of the insulin-to-growth hormone ratio on body composition of mice.
Am J Physiol.
1980;
238
E231-E234
- 16
Jeffcoate W.
Growth hormone therapy and its relationship to insulin resistance, glucose intolerance
and diabetes mellitus: a review of recent evidence.
Drug Saf.
2002;
25
199-212
- 17
Shulman D I.
Metabolic effects of growth hormone in the child and adolescent.
Curr Opin Pediatr.
2002;
14
432-436
- 18
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
- 19
Malmlof K, Johansen P B, Haahr P M, Wilken M, Oxlund H.
Methylprednisolone does not inhibit the release of growth hormone after intravenous
injection of a novel growth hormone secretagogue in rats.
Growth Horm IGF Res.
1999;
9
445-450
- 20
Johansen T, Deckert M, Mandrup-Poulsen T, Malmlof K.
The role of growth hormone and glucocorticoid in glucose handling in vivo.
.
J Endocrinol.
1999;
162
87-93
- 21
Lin X, Chavez M R, Bruch R C, Kilroy G E, Simmons L A, Lin L, Braymer H D, Bray G A,
York D A.
The effects of a high fat diet on leptin mRNA, serum leptin and the response to leptin
are not altered in a rat strain susceptible to high fat diet-induced obesity.
J Nutr.
1998;
128
1606-1613
- 22
Schwartz M W, Woods S C, Porte D, Seeley R J, Baskin D G.
Central nervous system control of food intake.
Nature.
2000;
404
661-671
- 23
van Dijk G.
The role of leptin in the regulation of energy balance and adiposity.
J Neuroendocrinol.
2001;
13
913-921
- 24
Masuzaki H, Ogawa Y, Hosoda K, Kawada T, Fushiki T, Nakao K.
Augmented expression of the obese gene in the adipose tissue from rats fed high-fat
diet.
Biochem Biophys Res Commun.
1995;
216
355-358
- 25
Stricker-Krongrad A, Cumin F, Burlet C, Beck B.
Hypothalamic neuropeptide Y and plasma leptin after long-term high-fat feeding in
the rat.
Neurosci Lett.
1998;
254
157-160
- 26
Roberts C K, Berger J J, Barnard R J.
Long-term effects of diet on leptin, energy intake, and activity in a model of diet-induced
obesity.
J Appl Physiol.
2002;
93
887-893
- 27
Steinberg G R, Dyck D J.
Development of leptin resistance in rat soleus muscle in response to high-fat diets.
Am J Physiol Endocrinol Metab.
2000;
279
E1374-E1382
- 28
Rolls B J, Rowe E A, Turner R C.
Persistent obesity in rats following a period of consumption of a mixed, high energy
diet.
J Physiol (Lond).
1980;
298
415-427
- 29
Azain M J, Hausman D B, Kasser T R, Martin R J.
Effect of somatotropin and feed restriction on body composition and adipose metabolism
in obese Zucker rats.
Am J Physiol.
1995;
269
E137-E144
- 30
al Shoumer K A, Gray R, Anyaoku V, Hughes C, Beshyah S, Richmond W, Johnston D G.
Effects of four years' treatment with biosynthetic human growth hormone (GH) on glucose
homeostasis, insulin secretion and lipid metabolism in GH-deficient adults.
Clin Endocrinol (Oxf).
1998;
48
795-802
- 31
Isozaki O, Tsushima T, Miyakawa M, Nozoe Y, Demura H, Seki H.
Growth hormone directly inhibits leptin gene expression in visceral fat tissue in
fatty Zucker rats.
J Endocrinol.
1999;
161
511-516
- 32
Karlsson C, Stenlof K, Johannsson G, Marin P, Bjorntorp P, Bengtsson B A, Carlsson B,
Carlsson L M, Sjostrom L.
Effects of growth hormone treatment on the leptin system and on energy expenditure
in abdominally obese men.
Eur J Endocrinol.
1998;
138
408-414
- 33
Garibotto G, Barreca A, Sofia A, Russo R, Fiorini F, Cappelli G, Cavatorta F, Cesarone A,
Franceschini R, Sacco P, Minuto F, Barreca T.
Effects of growth hormone on leptin metabolism and energy expenditure in hemodialysis
patients with protein-calorie malnutrition.
J Am Soc Nephrol.
2000;
11
2106-2113
- 34
Houseknecht K L, Portocarrero C P, Ji S, Lemenager R, Spurlock M E.
Growth hormone regulates leptin gene expression in bovine adipose tissue: correlation
with adipose IGF-1 expression.
J Endocrinol.
2000;
164
51-57
- 35
Cooling J, Barth J, Blundell J.
The high-fat phenotype: is leptin involved in the adaptive response to a high fat
(high energy) diet?.
Int J Obes Relat Metab Disord.
1998;
22
1132-1135
- 36
Walker C G, Bryson J M, Phuyal J L, Caterson I D.
Dietary modulation of circulating leptin levels: site-specific changes in fat deposition
and ob mRNA expression.
Horm Metab Res.
2002;
34
176-181
- 37
Ahren B.
Plasma leptin and insulin in C57BI/6J mice on a high-fat diet: relation to subsequent
changes in body weight.
Acta Physiol Scand.
1999;
165
233-240
- 38
Ahren B, Mansson S, Gingerich R L, Havel P J.
Regulation of plasma leptin in mice: influence of age, high-fat diet, and fasting.
Am J Physiol.
1997;
273
R113-R120
Dr. K. Malmlöf
Novo Nordisk A/S
Novo Nordisk Park · 2760 Malov · Denmark
Phone: +45 (44) 43 92 09 ·
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Email: kmal@novonordisk.com