Characterization of adipose tissue specific growth hormone receptor knockout mice

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 88-108-GHRH, GH & IGF Biology & Signaling
Basic/Translational
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-92
Edward Owen List*, Darlene E Berryman, Kevin Ray Funk, Adam Jara, Laura Kutz, Elizabeth Jensen, Wenjuan Zhang, Nicholas Lozier, Vincent Mikula, Alexandria Farrar, Ellen Muriel Richardson Lubbers, Katie Troike and John Joseph Kopchick
Ohio University, Athens, OH
In 1997, our laboratory generated growth hormone receptor knockout mice (GHRKO) (1).  Since then, these mice have been used in numerous studies and have proven to be an invaluable tool for uncovering the many and diverse actions of GH (2).  Many of these studies have pointed out the importance of GH in adipose tissue.  Thus, we selectively disrupted GHR in adipose tissue to produce Fat specific GHR Knock-Out mice (FaGHRKO) to better clarify the effects of GH adipose tissue in vivo.  We have recently published (3) that FaGHRKO mice are obese with increased adiposity occurring in all adipose depots.  Analysis of the adipose depots in these mice indicated that this obesity was due to increased adipocyte size. Unlike global GHRKO mice, FaGHRKO mice have no improvements in fasting blood glucose, insulin, glucose tolerance or insulin tolerance.  In FaGHRKO mice, circulating levels of adiponectin and resistin are unchanged (or slightly decreased) in contrast to global GHRKO mice which have increased levels. FaGHRKO mice also have decreased levels of adipsin and minimal changes to the GH/IGF-1 axis. Here we report on additional data obtained from both male and female FaGHRKO mice including: body composition data up to 2 years of age as well as circulating levels of cortisol, estradiol, progesterone, T3 and T4.  In conclusion, with the exception of increased adiposity, FaGHRKO mice share few similarities with global GHRKO mice.  Furthermore, our data suggests that certain previously thought direct actions of GH on adipose tissue are likely acting indirectly via GH action on other tissues which in turn affects adipose tissue.

(1) Zhou Y et al. A mammalian model for Laron syndrome produced by targeted disruption of the mouse growth hormone receptor/binding protein gene (the Laron mouse). Proc Natl Acad Sci USA 1997; 94:13215-13220. (2) List EO, et al. Endocrine parameters and phenotypes of the growth hormone receptor gene disrupted (GHR-/-) mouse. Endocr Rev 2011; 32:356-386. (3) List EO, et al. The Role of GH in Adipose Tissue: Lessons from Adipose-Specific GH Receptor Gene-Disrupted Mice. Mol Endocrinol. 2013; Jan 24. [Epub ahead of print]

Nothing to Disclose: EOL, DEB, KRF, AJ, LK, EJ, WZ, NL, VM, AF, EMRL, KT, JJK

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: 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, and by the Diabetes Institute at Ohio University.