title: Liver-specific GH receptor gene-disrupted (LiGHRKO) mice have decreased endocrine IGF-I, increased local IGF-I, and altered body size, body composition, and adipokine profiles.
abstract: GH is an important regulator of body growth and composition as well as numerous other metabolic processes. In particular, liver plays a key role in the GH/IGF-I axis, because the majority of circulating "endocrine" IGF-I results from GH-stimulated liver IGF-I production. To develop a better understanding of the role of liver in the overall function of GH, we generated a strain of mice with liver-specific GH receptor (GHR) gene knockout (LiGHRKO mice). LiGHRKO mice had a 90% decrease in circulating IGF-I levels, a 300% increase in circulating GH, and significant changes in IGF binding protein (IGFBP)-1, IGFBP-2, IGFBP-3, IGFBP-5, and IGFBP-7. LiGHRKO mice were smaller than controls, with body length and body weight being significantly decreased in both sexes. Analysis of body composition over time revealed a pattern similar to those found in GH transgenic mice; that is, LiGHRKO mice had a higher percentage of body fat at early ages followed by lower percentage of body fat in adulthood. Local IGF-I mRNA levels were significantly increased in skeletal muscle and select adipose tissue depots. Grip strength was increased in LiGHRKO mice. Finally, circulating levels of leptin, resistin, and adiponectin were increased in LiGHRKO mice. In conclusion, LiGHRKO mice are smaller despite increased local mRNA expression of IGF-I in several tissues, suggesting that liver-derived IGF-I is indeed important for normal body growth. Furthermore, our data suggest that novel GH-dependent cross talk between liver and adipose is important for regulation of adipokines in vivo.
authors: Edison Biotechnology Institute (E.O.L., D.E.B., K.F., A.J., B.K., E.A.J., W.Z., J.J.K.), Department of Specialty Medicine, Heritage College of Osteopathic Medicine (E.O.L.), School of Applied Health Sciences and Wellness (D.E.B.), Department of Biomedical Sciences, Heritage College of Osteopathic Medicine (D.E.B., A.J., J.J.K.), Ohio University, Athens, Ohio 45701-2942; Department of Internal Medicine (F.W., A.B.), Geriatrics Research, Southern Illinois University School of Medicine, Springfield, Illinois 62794-9628; Robert and Arlene Kogod Center on Aging (M.B.S., T.A.W., N.K.L., T.P., T.T., J.L.K.), Mayo Clinic, Rochester, Minnesota 55905-0002; College of Medicine, Burnett School of Biomedical Sciences (X.Z., M.M.M.), University of Central Florida, Orlando, Florida 32827-7406; and Department of Pathology and Geriatrics Center (L.S., R.A.M.), University of Michigan, Ann Arbor, Michigan 48109-2200.
authors: Edward O
authors: EO
authors: List
authors: Darlene E
authors: DE
authors: Berryman
authors: Kevin
authors: K
authors: Funk
authors: Adam
authors: A
authors: Jara
authors: Bruce
authors: B
authors: Kelder
authors: Feiya
authors: F
authors: Wang
authors: Michael B
authors: MB
authors: Stout
authors: Xu
authors: X
authors: Zhi
authors: Liou
authors: L
authors: Sun
authors: Thomas A
authors: TA
authors: White
authors: Nathan K
authors: NK
authors: LeBrasseur
authors: Tamara
authors: T
authors: Pirtskhalava
authors: Tamara
authors: T
authors: Tchkonia
authors: Elizabeth A
authors: EA
authors: Jensen
authors: Wenjuan
authors: W
authors: Zhang
authors: Michal M
authors: MM
authors: Masternak
authors: James L
authors: JL
authors: Kirkland
authors: Richard A
authors: RA
authors: Miller
authors: Andrzej
authors: A
authors: Bartke
authors: John J
authors: JJ
authors: Kopchick
mesh_terms: D054392:Adipokines / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000254:growth & development / Q000378:metabolism; D050154:Adiposity; D000375:Aging; D000818:Animals; D001823:Body Composition; D049628:Body Size; D004702:Endocrine Glands / Q000378:metabolism*; D005260:Female; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000254:growth & development / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000254:growth & development / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011986:Receptors, Somatotropin / Q000235:genetics / Q000378:metabolism*; D012727:Sex Characteristics; D015398:Signal Transduction
chemical_list: D054392:Adipokines; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone