Understanding the Metabolic Role of Growth Hormone: Mechanisms by which Growth Hormone Targets Adipocyte Structure and Function

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 649-677-Adipocyte Biology
Basic
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-674
Christopher Joseph Romero*1, Elisavet Agathou1, Ryan Scott Miller2, Andrew M Wolfe*3, Fredric Edward Wondisford4 and Sally Radovick4
1Johns Hopkins University School of Medicine, Baltimore, MD, 2Johns Hopkins Hospital, Baltimore, MD, 3Johns Hopkins Univ Schl of Med, Baltimore, MD, 4Johns Hopkins Med Instit, Baltimore, MD
Introduction: Growth hormone (GH) is well known for its role in growth and metabolic homeostasis. Growth hormone deficiency or excess demonstrate GH’s role in targeting adiposity and stimulating lipolysis, however, the mechanisms by which GH, under homeostatic conditions, helps to regulate adipose depots remains unclear. Using a knockout (ko) mouse model that produces a 4 fold increase in serum GH and overall decreased adiposity, we demonstrate increased energy expenditure of these mice as well changes in adipocyte histology in part by targeting and disrupting the balance between lipid synthesis and breakdown.

Methods and Results: Indirect calorimetry demonstrates that male somatotroph IGF-1 receptor knockout (SIGFRKO) mice have an overall increased RER with an elevated VO2 measurement vs controls (2806 ± 20.28 vs 2624 ± 26.18 ml/kg/hr, p<0.0001) during dark cycles, suggesting an overall increased basal metabolic rate. No significant differences in dark cycle activity (304.6 ± 12.93 vs 326.5 ± 14.05 counts) or total accumulated feed (3.847 ± 0.100 vs 3.964 ± 0.093 gm) were noted between groups. Heat production was only elevated during dark cycles (0.4541 ± 0.003 vs 0.4258 ± 0.004 kcal/hr, p<0.0001). The weights of dissected visceral, subcutaneous and brown adipose tissue (BAT) depots were less in SIGFRKO mice. Visceral adipocytes were significantly smaller (average adipocyte diameter, 30.04 ± 0.71 vs 48.32 ± 2.38, p<0.0001) as were the subcutaneous adipocytes (17.30 ± 0.49 vs 48.74 ± 4.29 µm) when compared to samples from control mice. Quantitative real time PCR of adipocyte cDNA shows increased gene expression in SIGFRKO BAT for hormone sensitive lipase (6 fold increase, p<0.01) and adipose triglyceride lipase. No significant differences in relative gene expression of fatty acid synthase and GLUT4 were noted between groups.

Conclusion: In the context of modestly elevated serum GH levels, we demonstrate that overall decreased adiposity can be attributed to GH targeting specific genes required for maintenance of adipocyte function. In addition, these mice demonstrate an increased metabolic rate despite no difference in food consumption or overall activity. Our model proves to be a useful tool in further understanding novel mechanisms by which GH contributes to the maintenance and regulation of metabolic homeostasis.

Disclosure: SR: Ad Hoc Consultant, CVS/Caremark, Speaker, Novo Nordisk. Nothing to Disclose: CJR, EA, RSM, AMW, FEW

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

Sources of Research Support: NIH/NIDDK - Mentored Clinical Scientist Research Career Development Award K08 (1K08DK088996-01A1) awarded to CJR.