Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment

Heffernan, Mark; Thorburn, Anne W.; Fam, Barbara C; Summers, Roger J.; Conway-Campbell, Becky; Waters, Michael J.; Ng, Frank M

doi:10.1038/sj.ijo.0801740

Cited by 29 publications

(37 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is of interest that also smaller GH fragments stimulate energy expenditure and induce weight loss in animals (39). Intact GH may induce insulin resistance, at least initially.…”

Section: Effect Of Growth Hormone Therapy On Body Weight and Body Commentioning

confidence: 99%

Obesity, growth hormone and weight loss

Rasmussen

2010

Molecular and Cellular Endocrinology

105

View full text Add to dashboard Cite

Growth hormone (GH) is the most important hormonal regulator of postnatal longitudinal growth in man. In adults GH is no longer needed for longitudinal growth. Adults with growth hormone deficiency (GHD) are characterised by perturbations in body composition, lipid metabolism, cardiovascular risk profile and bone mineral density. It is well established that adult GHD usually is accompanied by an increase in fat accumulation and GH replacement in adult patients with GHD results in reduction of fat mass and abdominal fat mass in particular. It is also recognized that obesity and abdominal obesity in particular results in a secondary reduction in GH secretion and subnormal insulin-like growth factor-I (IGF-I) levels. The recovery of the GH IGF-I axis after weight loss suggest an acquired defect, however, the pathophysiologic role of GH in obesity is yet to be fully understood. In clinical studies examining the efficacy of GH in obese subjects very little or no effect are observed with respect to weight loss, whereas GH seems to reduce total and abdominal fat mass in obese subjects. The observed reductions in abdominal fat mass are modest and similar to what can be achieved by diet or exercise interventions.

show abstract

“…It is of interest that also smaller GH fragments stimulate energy expenditure and induce weight loss in animals (39). Intact GH may induce insulin resistance, at least initially.…”

Section: Effect Of Growth Hormone Therapy On Body Weight and Body Commentioning

confidence: 99%

Obesity, growth hormone and weight loss

Rasmussen

2010

Molecular and Cellular Endocrinology

105

View full text Add to dashboard Cite

show abstract

“…[4][5][6][7] Clinical and experimental investigations have shown that GH administration leads to the reduction in fat mass in GH-deficient individuals as well as individuals suffering from certain genetic forms of obesity, such as Prader-Willi syndrome, and in obese animal models, such as ob/ob mice, which display diminished GH secretion. [8][9][10][11] However, despite these positive effects of GH on adipose reduction, GH treatments of individuals with idiopathic obesity (not associated with an endocrinopathy or syndrome) have had little success, even though their GH levels are generally reduced. 12 These observations suggest that idiopathic obesity may be associated with GH resistance at the level of the adipocyte because of altered GHR expression.…”

Section: Introductionmentioning

confidence: 99%

Human growth hormone receptor (GHR) expression in obesity: I. GHR mRNA expression in omental and subcutaneous adipose tissues of obese women

2011

View full text Add to dashboard Cite

Objectives: Growth hormone (GH)-deficient individuals display increased adiposity that can be effectively reduced by GH therapy because of GH's lipolytic effects. However, similar GH treatments of individuals with idiopathic obesity (not associated with an endocrinopathy/syndrome) have had little success. We hypothesized that this form of obesity may be associated with GH resistance at the level of the adipocyte because of reduced GH receptor (GHR) expression. Subjects and methods: We studied GHR expression in omental and subcutaneous fat tissues from a cohort of 55 women ranging from lean to obese by various adiposity parameters. mRNA levels of total GHR and the dominant-negative truncated GHR 1À279 (trGHR) form were assayed by quantitative reverse transcriptase-PCR. Associations between adiposity measures and GHR levels as well as trGHR/GHR ratios were analyzed. Results: Total GHR mRNA expression was 2-3-fold lower in omental as well as subcutaneous adipose tissues of obese compared with lean women (Pp0.05-0.001). Lean individuals expressed higher GHR mRNA levels in omental fat compared with subcutaneous (Pp0.01); in obese women, this depot-specific difference was lost. Omental and subcutaneous adipose GHR mRNA levels displayed significant negative correlations with a spectrum of indicators of obesity while, in subcutaneous fat, there was a significantly higher trGHR/GHR ratio with increasing adiposity (Pp0.05). Conclusion: These results support our hypothesis that, with obesity, there is lower GHR expression in the adipocyte, and suggest one possible explanation why GH supplementation is not an effective treatment for individuals with idiopathic obesity.

show abstract

“…34,35 The literature search furthermore identified 13 animal experiments qualifying for review. [36][37][38][39][40][41][42][43][44][45][46][47][48] The results in the text are reported as mean ± SEM unless otherwise noted.…”

Section: Literature Reviewmentioning

confidence: 99%

Treatment of Obesity Using GH

Johansen

Malmlöf²

2006

Metabolic Syndrome and Related Disorders

View full text Add to dashboard Cite

The obesity epidemic calls for complementary treatment possibilities in addition to lifestyle changes. One of the important regulators of lipid homeostasis is growth hormone (GH). Clinical trials have tested if GH can reduce obesity in humans. The mechanisms underlying the response to GH administration have also been investigated in animal models of human obesity. A literature search yielded 19 randomized placebo-controlled clinical studies and several animal studies investigating chronic GH treatment of obesity. Significant effects were found in some of the larger trials. One clinical trial showed significantly increased weight loss due to GH treatment, and in seven trials, a significant reduction of fat mass was found. The improvements observed were modest, but even minor improvements have been shown to be beneficial, especially if the reduction in fat mass includes visceral adipose tissue, as was reported in three of six trials. In principle, animal data support the clinical observations although the reduction of fat mass was more dramatic than observed in humans. The mechanisms resulting in lipid mobilization most likely include adipose tissue lipo-protein lipase (LPL) inhibition and antagonization of the anti-lipolytic activity of insulin. By feeding a restricted amount of a high fat diet to GH exposed rats hyper-insulinemia was avoided, loss of body fat was accelerated and metabolic markers were improved. Provision of a diet suitable for the metabolic conditions during GH treatment shows promise for improving metabolic control and can perhaps increase the efficacy and/or widen the therapeutic window of GH.

show abstract

Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment

Cited by 29 publications

References 29 publications

Obesity, growth hormone and weight loss

Obesity, growth hormone and weight loss

Human growth hormone receptor (GHR) expression in obesity: I. GHR mRNA expression in omental and subcutaneous adipose tissues of obese women

Treatment of Obesity Using GH

Contact Info

Product

Resources

About