Developments in our understanding of the effects of growth hormone on white adipose tissue from mice: implications to the clinic

ABSTRACT

Adipose tissue (AT) is a well-established target of growth hormone (GH) and is altered in clinical conditions associated with excess, deficiency and absence of GH action. Due to the difficulty in collecting AT from clinical populations, genetically modified mice have been useful in better understanding how GH affects this tissue. Recent findings in mice would suggest that the impact of GH on AT is beyond alterations of lipolysis, lipogenesis or proliferation/ differentiation. AT depot-specific alterations in immune cells, extracellular matrix, adipokines, and senescence indicate an expanded role for GH in AT physiology. These mouse data will guide additional studies necessary to evaluate the therapeutic potential and safety of GH for conditions associated with altering AT, such as obesity. In this review, we introduce several relatively new intricacies of GH’s effect on AT, focusing on recent studies in mice. Finally, we summarize the clinical implications of these findings.

KEYWORDS:

• Growth hormone
• adipose tissue
• Laron Syndrome
• acromegaly
• growth hormone deficiency
• obesity
• bGH mice
• GHR-/- mice
• GHA mice
• Ames dwarf

Financial and competing interests disclosure

This work was supported by NIH grant P01AG031736, by the State of Ohio’s Eminent Scholar Program that includes a gift from Milton and Lawrence Goll, by the AMVETS received by J. Kopchick, and by the Diabetes Institute at Ohio University. D. Berryman and E. List received a Grant for Growth Innovation from Merck Serano. R. Hjortebjerg is with the Danish Diabetes Academy, which is supported by the Novo Nordisk Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Adipose tissue (AT) is significantly more complex than previously thought, requiring one to reevaluate how a hormone, such as growth hormone (GH), alters the tissue.

• Clinical disorders associated with excess, decrease or absence of GH action, such as acromegaly, growth hormone deficiency and Laron syndrome, respectively, are associated with significant alterations in AT mass and adipokine profiles.

• Mouse lines with altered GH action provide a useful means for a comparative analysis of GH action in AT as well as clinical disorders associated with GH action (LS, GHD and acromegaly).

• GH is an important regulator of AT metabolism well documented to decrease AT mass through stimulating lipolysis, inhibiting lipogenesis, and affecting adipocyte proliferation and differentiation. However, newer finding in mice reveal new ways in which GH alters AT including endocrine regulation, senescence, immune cell modulation and extracellular matrix deposition.

• Findings from clinical populations with altered GH action and animal models confirm that GH does not alter AT uniformly with subQ and visceral AT differentially impacted and that as GH decreases the quantity of fat, the quality of AT may be compromised.

• Obese patients present with a markedly suppressed spontaneous as well as stimulated GH secretion.GH treatment of obese subjects has little effect on bodyweight. However, visceral depot size is decreased and metabolic profile is generally improved. Based on mouse data, the health of the AT with GH treatment is likely compromised.