Effects of 14-day infusions of growth hormone and/or insulin-like growth factor I on the obesity of growing Zucker rats

被引:7
作者
Dubuis, JM
Deal, C
Tsagaroulis, P
Clark, RG
VanVliet, G
机构
[1] HOP ST JUSTINE, UNIT REPROD & DEV BIOL, RES CTR, MONTREAL, PQ H3T 1C5, CANADA
[2] UNIV MONTREAL, DEPT PEDIAT, MONTREAL, PQ H3T 1C5, CANADA
[3] GENENCOR INC, DEPT ENDOCRINE RES, S SAN FRANCISCO, CA 94080 USA
关键词
D O I
10.1210/en.137.7.2799
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The response of fat tissue to GH or insulin-like growth factor I (IGF-I) differs between humans with hypopituitarism and those with exogenous obesity; the effects of combined GH and IGF-I administration have not been compared in these two situations. In GH-deficient dwarf rats (who have a primary GH deficiency), the excessive fat deposition induced by a high fat diet is completely reversed by combined infusion of GH and IGF-I. Whether the same phenomenon would be observed in genetically obese Zucker rats (in whom, as in obese humans, the decrease in GH secretion is secondary to the obese state) remained to be determined. Growing (6-week-old) female obese Zucker rats received a continuous sc infusion of vehicle, recombinant human GH, recombinant human IGF-I, or GH plus IGF-I for 14 days (3 mg/kg day for both GH and IGF-I). Combined GH and IGF-I stimulated body weight gain and growth in naso-anal length to the same extent as IGF-I alone, whereas GH alone was less potent. Because all treatments stimulated weight and linear growth proportionately, the progression of obesity was similar in treated and control animals. However, GH plus IGF-I (but not either agent alone) induced a 25% decrease in the relative weight of inguinal fat. GH and IGF-I exerted distinct effects on the relative weights of liver, kidney, and spleen and on the circulating levels of IGF-I and IGF-binding protein-3. Circulating glucose and insulin levels did not change in any group. In summary, GH plus IGF-I infusions decrease the relative weight of inguinal fat in Zucker rats as in obese GH-deficient dwarf rats; however, this effect is of more modest magnitude despite the use of a 2- to 3-fold higher dose and is limited to the inguinal site. Thus, GH plus IGF-I infusions did not influence the obesity index in Zucker rats. Inasmuch as Zucker rats are a better model of childhood-onset obesity than dwarf rats fed a high fat diet, the present results do not appear promising for extrapolation to clinical studies in children. The mechanisms by which the primary vs. secondary nature of the decreased GH secretion influences the effect of GH plus IGF-I on obesity remain to be determined.
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页码:2799 / 2806
页数:8
相关论文
共 39 条
[1]   DEVELOPMENTAL-CHANGES IN LEVELS OF GROWTH-HORMONE MESSENGER-RNA IN ZUCKER RATS [J].
AHMAD, I ;
STEGGLES, AW ;
CARRILLO, AJ ;
FINKELSTEIN, JA .
JOURNAL OF CELLULAR BIOCHEMISTRY, 1990, 43 (01) :59-66
[2]   EFFECT OF SOMATOTROPIN AND FEED RESTRICTION ON BODY-COMPOSITION AND ADIPOSE METABOLISM IN OBESE ZUCKER RATS [J].
AZAIN, MJ ;
HAUSMAN, DB ;
KASSER, TR ;
MARTIN, RJ .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 1995, 269 (01) :E137-E144
[3]  
BAXTER RC, 1991, ADV EXP MED BIOL, V293, P125
[4]   CORRELATION BETWEEN LEE INDEX AND CARCASS FAT CONTENT IN WEANLING AND ADULT FEMALE RATS WITH HYPOTHALAMIC LESIONS [J].
BERNARDIS, LL ;
PATTERSON, BD .
JOURNAL OF ENDOCRINOLOGY, 1968, 40 (04) :527-+
[5]   GENETIC AND NONGENETIC DETERMINANTS OF REGIONAL FAT DISTRIBUTION [J].
BOUCHARD, C ;
DESPRES, JP ;
MAURIEGE, P .
ENDOCRINE REVIEWS, 1993, 14 (01) :72-93
[6]   Phenotypes of mouse diabetes and rat fatty due to mutations in the OB (leptin) receptor [J].
Chua, SC ;
Chung, WK ;
WuPeng, XS ;
Zhang, YY ;
Liu, SM ;
Tartaglia, L ;
Leibel, RL .
SCIENCE, 1996, 271 (5251) :994-996
[7]   The obese growth hormone (GH)-deficient dwarf rat: Body fat responses to patterned delivery of GH and insulin-like growth factor-I [J].
Clark, RG ;
Mortensen, DL ;
Carlsson, LMS ;
Carlsson, B ;
Carmignac, D ;
Robinson, ICAF .
ENDOCRINOLOGY, 1996, 137 (05) :1904-1912
[8]   Serum immunoreactive leptin concentrations in normal-weight and obese humans [J].
Considine, RV ;
Sinha, MK ;
Heiman, ML ;
Kriauciunas, A ;
Stephens, TW ;
Nyce, MR ;
Ohannesian, JP ;
Marco, CC ;
McKee, LJ ;
Bauer, TL ;
Caro, JF .
NEW ENGLAND JOURNAL OF MEDICINE, 1996, 334 (05) :292-295
[9]   INSULIN-LIKE GROWTH FACTOR-I AND FACTOR-II - PEPTIDE, MESSENGER RIBONUCLEIC-ACID AND GENE STRUCTURES, SERUM, AND TISSUE CONCENTRATIONS [J].
DAUGHADAY, WH ;
ROTWEIN, P .
ENDOCRINE REVIEWS, 1989, 10 (01) :68-91
[10]   EFFECT OF GROWTH-HORMONE ON CARBOHYDRATE AND LIPID-METABOLISM [J].
DAVIDSON, MB .
ENDOCRINE REVIEWS, 1987, 8 (02) :115-131