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

    Authors

    E. O. List; D. E. Berryman; K. Funk; A. Jara; B. Kelder; F. Wang; M. B. Stout; X. Zhi; L. Sun; T. A. White; N. K. LeBrasseur; T. Pirtskhalava; T. Tchkonia; E. A. Jensen; W. J. Zhang; M. M. Masternak; J. L. Kirkland; R. A. Miller; A. Bartke;J. J. Kopchick

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    Abbreviated Journal Title

    Endocrinology

    Keywords

    GROWTH-FACTOR-I; DIET-INDUCED OBESITY; PROTEIN KNOCKOUT MICE; INSULIN; SENSITIVITY; FATTY LIVER; ADIPOSE-TISSUE; GLUCOSE-HOMEOSTASIS; CRE; RECOMBINASE; MOUSE GROWTH; DWARF MICE; Endocrinology & Metabolism

    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.

    Journal Title

    Endocrinology

    Volume

    155

    Issue/Number

    5

    Publication Date

    1-1-2014

    Document Type

    Article

    Language

    English

    First Page

    1793

    Last Page

    1805

    WOS Identifier

    WOS:000342342200022

    ISSN

    0013-7227

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