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  • Review Article
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The GH/IGF-1 axis in obesity: pathophysiology and therapeutic considerations

Nature Reviews Endocrinology volume 9, pages 346–356 (2013)Cite this article

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Abstract

Obesity has become one of the most common medical problems in developed countries, and this disorder is associated with high incidences of hypertension, dyslipidaemia, cardiovascular disease, type 2 diabetes mellitus and specific cancers. Growth hormone (GH) stimulates the production of insulin-like growth factor 1 in most tissues, and together GH and insulin-like growth factor 1 exert powerful collective actions on fat, protein and glucose metabolism. Clinical trials assessing the effects of GH treatment in patients with obesity have shown consistent reductions in total adipose tissue mass, in particular abdominal and visceral adipose tissue depots. Moreover, studies in patients with abdominal obesity demonstrate a marked effect of GH therapy on body composition and on lipid and glucose homeostasis. Therefore, administration of recombinant human GH or activation of endogenous GH production has great potential to influence the onset and metabolic consequences of obesity. However, the clinical use of GH is not without controversy, given conflicting results regarding its effects on glucose metabolism. This Review provides an introduction to the role of GH in obesity and summarizes clinical and preclinical data that describe how GH can influence the obese state.

Key Points

  • Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) signalling plays a major part in fuel metabolism and in the regulation of body composition

  • Obesity, particularly abdominal obesity, exerts a strong negative effect on the spontaneous pulsatile secretion of GH, which has been associated with adverse metabolic complications

  • GH administration in individuals with abdominal obesity reduces visceral and total body adipose tissue mass, as well as levels of total and LDL cholesterol

  • Increasing the endogenous pulsatile GH secretion in individuals with obesity has metabolic effects similar to those obtained by the administration of exogenous GH but potentially with less adverse effects on glucose metabolism

  • Mouse models with altered GH signalling provide a useful means for a comparative analysis of GH action in obesity

  • The role of the GH/IGF-1 axis in modifying obesity must be assessed in light of newly emerging data that highlight the complexity of adipose tissue

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Figure 1: Effects of the interaction between GH, IGF-1, FFAs and insulin on adipose tissue, liver and skeletal muscle.
Figure 2: Schematic representation of potential depot-specific differences between subcutaneous and visceral adipose tissue in mice with normal GH signalling, low GH signalling (such as Ghr−/− mice) or increased GH signalling (such as GH transgenic mice).

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Authors and Affiliations

  1. Edison Biotechnology Institute, Ohio University, 1 Water Tower Drive, The Ridges, Athens, 45701, OH, USA

    Darlene E. Berryman & Edward O. List

  2. Department of Endocrinology, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gröna stråket 8, Gothenburg, SE-413 45, Sweden

    Camilla A. M. Glad & Gudmundur Johannsson

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G. Johannsson declares that he has received speaking honoraria and grant support from the following companies: Novo Nordisk, Pfizer. The other authors declare no competing interests.

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Berryman, D., Glad, C., List, E. et al. The GH/IGF-1 axis in obesity: pathophysiology and therapeutic considerations. Nat Rev Endocrinol 9, 346–356 (2013). https://doi.org/10.1038/nrendo.2013.64

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