The Role of GH in Adipose Tissue: Lessons from Adipose-Specific GH Receptor Gene-Disrupted Mice

Abstract

GH receptor (GHR) gene-disrupted mice (GHR-/-) have provided countless discoveries as to the numerous actions of GH. Many of these discoveries highlight the importance of GH in adipose tissue. For example GHR-/- mice are insulin sensitive yet obese with preferential enlargement of the sc adipose depot. GHR-/- mice also have elevated levels of leptin, resistin, and adiponectin, compared with controls leading some to suggest that GH may negatively regulate certain adipokines. To help clarify the role that GH exerts specifically on adipose tissue in vivo, we selectively disrupted GHR in adipose tissue to produce Fat GHR Knockout (FaGHRKO) mice. Surprisingly, FaGHRKOs shared only a few characteristics with global GHR-/- mice. Like the GHR-/- mice, FaGHRKO mice are obese with increased total body fat and increased adipocyte size. However, FaGHRKO mice have increases in all adipose depots with no improvements in measures of glucose homeostasis. Furthermore, resistin and adiponectin levels in FaGHRKO mice are similar to controls (or slightly decreased) unlike the increased levels found in GHR-/- mice, suggesting that GH does not regulate these adipokines directly in adipose tissue in vivo. Other features of FaGHRKO mice include decreased levels of adipsin, a near-normal GH/IGF-1 axis, and minimal changes to a large assortment of circulating factors that were measured such as IGF-binding proteins. In conclusion, specific removal of GHR in adipose tissue is sufficient to increase adipose tissue and decrease circulating adipsin. However, removal of GHR in adipose tissue alone is not sufficient to increase levels of resistin or adiponectin and does not alter glucose metabolism.

Differential impact of selective GH deficiency and endogenous GH excess on insulin-mediated actions in muscle and liver of male mice

“…This is consistent with reports showing GH treatment suppresses insulin-induced glucose uptake in muscle in normal human subjects (20). Although the current study was not designed to investigate the cellular mechanism of GH-mediated inhibition of muscle glucose uptake, our current results suggest skeletal muscles are more sensitive than adipose tissue to changes in endogenous GH levels, with respect to insulin-mediated glucose uptake, as suggested by data generated by others (21,33).…”

Targeted Deletion of Growth Hormone (GH) Receptor in Macrophage Reveals Novel Osteopontin-mediated Effects of GH on Glucose Homeostasis and Insulin Sensitivity in Diet-induced Obesity

“…Specifically, our studies establish that on a HFD, lack of GH action on the M⌽ results in preferential accumulation of M1-polarized M⌽ in adipose tissue. It is noteworthy that a recent study reported that targeted ablation of GHR expression in adipose tissue in mouse did not alter glucose metabolism on a normal diet (38). These results were obtained on a normal diet and it would be of interest to compare the effect of GH action on adipose tissue versus adipose tissue macrophage on a high fat diet.…”

The Associations of GH and GHR Genes with Carcass Components in Indonesian Kampung and Broiler Chicken Cross

“…The GH molecule has two binding sites which each interacts with the extracellular region of the performed GHR dimer. This binding leads a functionally dimerized complex that induces intracellular signaling (Kopchick, 2016;List et al, 2013). The GH-GHR complexes are then resulted in the endoplasmic reticulum (van den Eijnden & Strous, 2007).…”