The role of GH in adipose tissue: lessons from adipose-specific GH receptor gene-disrupted mice.
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.
Edison Biotechnology Institute, Athens, OH 45701, USA.
Edward O
EO
List
Darlene E
DE
Berryman
Kevin
K
Funk
Elahu S
ES
Gosney
Adam
A
Jara
Bruce
B
Kelder
Xinyue
X
Wang
Laura
L
Kutz
Katie
K
Troike
Nicholas
N
Lozier
Vincent
V
Mikula
Ellen R
ER
Lubbers
Han
H
Zhang
Clare
C
Vesel
Riia K
RK
Junnila
Stuart J
SJ
Frank
Michal M
MM
Masternak
Andrzej
A
Bartke
John J
JJ
Kopchick
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D054392:Adipokines / Q000097:blood; D000273:Adipose Tissue / Q000378:metabolism*; D050154:Adiposity; D000818:Animals; D001823:Body Composition; D001835:Body Weight; D002452:Cell Count; D048429:Cell Size; D016207:Cytokines / Q000097:blood; D005260:Female; D017353:Gene Deletion; D005947:Glucose / Q000378:metabolism; D013006:Growth Hormone / Q000378:metabolism*; D006706:Homeostasis; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009929:Organ Size; D009928:Organ Specificity; D011986:Receptors, Somatotropin / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
D054392:Adipokines; D016207:Cytokines; D018969:Insulin-Like Growth Factor Binding Proteins; D011986:Receptors, Somatotropin; D014280:Triglycerides; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D005947:Glucose