<b>Low‐dose growth hormone replacement lowers plasma leptin and fat stores without affecting body mass index in adults with growth hormone deficiency</b>

Florkowski, Chris; Collier, Gregory; Zimmet, P; Livesey, J. H.; Espiner, Eric A.; Donald, R. A.

doi:10.1046/j.1365-2265.1996.830895.x

Cited by 101 publications

(78 citation statements)

References 17 publications

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“…In the whole dataset, 24-h leptin levels were the principal correlates of 24-h GH levels and they changed consensually following weight loss. Several authors 35,36 have reported that GH supplementation in GH-deficient adult patients decreased both body fat and plasma leptin concentrations. Moreover, Isokazi et al 37 showed in Zucker fa/fa rats that GH directly inhibits leptin gene expression in visceral fat tissue.…”

Section: Discussionmentioning

confidence: 99%

Daylong pituitary hormones in morbid obesity: effects of bariatric surgery

et al. 2008

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Moderate obesity is known to be associated with multiple endocrine abnormalities. Less information is available on the hormonal status of patients with morbid obesity and on the effects of major weight loss. We studied 16 severely obese (BMI 40.6-69.9 kg/m 2 ) nondiabetic patients and 7 nonobese (BMI range 24.6-27.7 kg/m 2 ), sex-and age-matched healthy volunteers. During 24 h in a metabolic ward, four meals were administered and hourly blood samples were drawn from a central venous catheter for the measurement of glucose, insulin, leptin, thyrotropic hormone (TSH), growth hormone (GH) and prolactin. Insulin sensitivity was measured by a euglycaemic hyperinsulinaemic clamp. Studies were repeated 6 months after biliopancreatic diversion, a mainly malabsorptive surgical approach, which caused an average weight loss of 35±4 kg (or 26 ± 2% of initial weight). Compared with controls, patients were hyperinsulinaemic (290 ± 31 vs 88 ± 4 pmol l À1 , P ¼ 0.0002), insulin resistant (23.5±2.8 vs 52.9±4.9 mmol min À1 kg FFM À1 , P ¼ 0.0006) and hyperleptinaemic (52.5±5.8 vs 10.9±3 ng ml À1 , P ¼ 0.0002). Plasma TSH levels were increased throughout the day-night cycle (averaging 2.02 ± 0.18 vs 1.09 ± 0.19 mU ml À1 of controls, P ¼ 0.01), whereas serum GH levels were suppressed (0.46±0.10 vs 3.01±1.15, P ¼ 0.002). Following surgery, the hyperinsulinaemia and insulin resistance were fully normalized; in concomitance with a major drop in leptin levels (to 14.4±2.7 ng ml À1 , P ¼ 0.02), TSH decreased and GH increased to near-normal levels. In the whole dataset, mean 24-h leptin levels were directly related to mean 24-h TSH levels after controlling for confounders this relationship was lost only after adjusting for fat mass. We conclude that in morbid obesity leptin is a determinant of changes in pituitary function.

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Section: Discussionmentioning

confidence: 99%

Daylong pituitary hormones in morbid obesity: effects of bariatric surgery

et al. 2008

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“…Leptin is another regulator of the GH-IGF-I axis. In rodents, leptin stimulated GH release 36 and in human elevated serum leptin in hypopituitary patients was reduced by GH treatment. 37,38 Thus an elevated leptin level and low GH level would fit the concept of a leptin resistance in obese subjects.…”

Section: Discussionmentioning

confidence: 99%

Relationship between reduced serum IGF-I levels and accumulation of visceral fat in Japanese men

et al. 2002

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OBJECTIVE:To investigate whether the changes in IGF-I concentrations after weight reduction in Japanese overweight men are associated with changes in visceral and subcutaneous fat. DESIGN: Cross-sectional and longitudinal clinical intervention study with exercise education. SUBJECTS: One-hundred and twelve Japanese overweight men aged 30 -59 y (body mass index (BMI) 28.4 AE 2.5 kg=m 2 ) and 33 normal-weight men aged 30 -39 y (BMI 22.1 AE 1.5 kg=m 2 ) at baseline. From the participants, 56 randomly selected overweight men (BMI 28.8 AE 2.8) were further enrolled into a 1 y exercise program. MEASUREMENTS: Fat distribution was evaluated by visceral fat (V) and subcutaneous fat (S) areas measured with computed tomography scanning at umbilical levels, metabolic parameters and hormones including insulin, leptin and IGF-I at baseline and after 1 y. RESULTS: In 112 overweight subjects at baseline, insulin (10.5 AE 5.0 mU=ml) and leptin (6.4 AE 3.7 ng=ml) significantly correlated with both V (r ¼ 0.260, P ¼ 0.0073; r ¼ 0.410, P < 0.0001) and S areas (r ¼ 0.377, P < 0.0001; r ¼ 0.613, P < 0.0001), respectively. IGF-I (156.8 AE 48.7 mU=ml) significantly and negatively correlated with V area (r ¼ 7 0.242, P ¼ 0.0125) and age (r ¼ 7 0.192, P ¼ 0.0480). In normal-weight men aged 30 -39 y (n ¼ 33) and age-matched subjects (n ¼ 30) selected from the 112 overweight men, the serum IGF-I further tightly correlated with V area (r ¼ 7 0.467, P < 0.0001). Visceral fat area and age were independently related to serum IGF-I levels by multiple regression analysis. By intervention with exercise education, 56 overweight subjects showed an increase in daily steps (6224 AE 2781 to 7898 AE 4141 steps=day) and reduction of BMI (28.8 AE 2.8 to 27.7 AE 2.9). DIGF-I significantly correlated with DV area (r ¼ 7 0.432, P ¼ 0.0009) but not with DS area or DBMI. CONCLUSION: The present study indicated a negative correlation between IGF-I levels and visceral fat at baseline as well as an association between the reduction in visceral fat and increase in IGF-I levels after an exercise intervention.

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“…60,61 This function is chie¯y accomplished by decreasing food consumption, 62,63 an effect probably mediated through inhibition of neuropeptide Y (NPY) secretion 64 ± 66 and enhancement of energy expenditure. 67,68 Indeed, serum leptin levels are elevated in simple obesity 69 and in clinical conditions associated with increased body fat such as Cushing's syndrome 70 and adult GH de®ciency, 71,72 and low in anorexia nervosa. 73,74 On the other side, GH also takes part in the regulation of body composition through a marked nitrogen sparing and lipolytic effect, 75 as shown by its administration to obese 76 and GH de®cient patients.…”

Section: Leptin As a Peripheral Signal For Gh Regulationmentioning

confidence: 99%

Growth hormone in obesity

1999

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Growth hormone (GH) secretion, either spontaneous or evoked by provocative stimuli, is markedly blunted in obesity. In fact obese patients display, compared to normal weight subjects, a reduced half-life, frequency of secretory episodes and daily production rate of the hormone. Furthermore, in these patients GH secretion is impaired in response to all traditional pharmacological stimuli acting at the hypothalamus (insulin-induced hypoglycaemia, arginine, galanin, L-dopa, clonidine, acute glucocorticoid administration) and to direct somatotrope stimulation by exogenous growth hormone releasing hormone (GHRH). Compounds thought to inhibit hypothalamic somatostatin (SRIH) release (pyridostigmine, arginine, galanin, atenolol) consistently improve, though do not normalize, the somatotropin response to GHRH in obesity. The synthetic growth hormone releasing peptides (GHRPs) GHRP-6 and hexarelin elicit in obese patients GH responses greater than those evoked by GHRH, but still lower than those observed in lean subjects. The combined administration of GHRH and GHRP-6 represents the most powerful GH releasing stimulus known in obesity, but once again it is less effective in these patients than in lean subjects. As for the peripheral limb of the GH ± insulin-like growth factor I (IGF-I) axis, high free IGF-I, low IGF-binding proteins 1 (IGFBP-1) and 2 (IGFBP-2), normal or high IGFBP-3 and increased GH binding protein (GHBP) circulating levels have been described in obesity. Recent evidence suggests that leptin, the product of adipocyte speci®c ob gene, exerts a stimulating effect on GH release in rodents; should the same hold true in man, the coexistence of high leptin and low GH serum levels in human obesity would ®t in well with the concept of a leptin resistance in this condition. Concerning the in¯uence of metabolic and nutritional factors, an impaired somatotropin response to hypoglycaemia and a failure of glucose load to inhibit spontaneous and stimulated GH release are well documented in obese patients; furthermore, drugs able to block lipolysis and thus to lower serum free fatty acids (NEFA) signi®cantly improve somatotropin secretion in obesity. Caloric restriction and weight loss are followed by the restoration of a normal spontaneous and stimulated GH release. On the whole, hypothalamic, pituitary and peripheral factors appear to be involved in the GH hyposecretion of obesity. A SRIH hypertone, a GHRH de®ciency or a functional failure of the somatotrope have been proposed as contributing factors. A lack of the putative endogenous ligand for GHRP receptors is another challenging hypothesis. On the peripheral side, the elevated plasma levels of NEFA and free IGF-I may play a major role. Whatever the cause, the defect of GH secretion in obesity appears to be of secondary, probably adaptive, nature since it is completely reversed by the normalization of body weight. In spite of this, treatment with biosynthetic GH has been shown to improve the body composition and the metabolic ef®cacy of lean body mass in obese pa...

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Low‐dose growth hormone replacement lowers plasma leptin and fat stores without affecting body mass index in adults with growth hormone deficiency

Abstract: Plasma leptin and total body fat fall promptly in response to low-dose replacement of GH in GH-deficient subjects. Hormone-induced changes in leptin can occur in humans in the absence of change in body mass index.

Cited by 101 publications

References 17 publications

Daylong pituitary hormones in morbid obesity: effects of bariatric surgery

Daylong pituitary hormones in morbid obesity: effects of bariatric surgery

Relationship between reduced serum IGF-I levels and accumulation of visceral fat in Japanese men

Growth hormone in obesity

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