Effects of growth hormone-releasing hormone (GHRH) gene targeted ablation on adipose tissue, feeding and adipokine gene expression in mice

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 649-659-Basic Mechanisms of Obesity
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-655
Luigi Brunetti*1, Rugia Shohreh2, Lucia Recinella1, Claudio Ferrante2, Sheila Leone3, Annalisa Chiavaroli2, Chiara Di Nisio1, Adriana Ricciuti4, Fabio Manippa5, Giustino Orlando5, Roberto Salvatori6 and Michele Vacca5
1G. D'Annunzio University, Chieti, Italy, 2G. d'Annunzio University, Chieti, Italy, 3G.D'Annunzio University, Chieti, Italy, 4G. d'Annunzio University, Chieti, 5G.d'Annunzio University, Chieti, 6Johns Hopkins Univ Sch of Med, Baltimore, MD
Context: Growth hormone (GH) deficiency (GHD) leads to growth failure and significant changes in body composition including increased fat accumulation and reduced lean body mass in both humans and rodents [1].

Objectives: The aim of this study was to characterize the consequences of GHD on adiposity, total body weight (TBW), and food intake in a mouse model of autosomal recessive isolated GHD due to targeted ablation of the GH-releasing hormone (GHRH) gene [GHRH knockout (GHRHKO)]. Animals were also analyzed with respect to leptin, adiponectin and visfatin gene expression in both intra-abdominal  and subcutaneous fat.

Design: We studied 8 male mice homozygous for GHRHKO allele (-/-) and 8 male heterozygous animals (+/-) as controls. Feeding and TBW data were collected weekly beginning 3 months through 5 months of age, after which animals were sacrificed. Body length (nose-anus distance, N-A), intra-abdominal (epididymal and retroperitoneal) and subcutaneous (inguinal) fat weights were measured. Total RNA was extracted from both intra-abdominal and subcutaneous fat and reverse transcribed to evaluate gene expression of leptin, adiponectin and visfatin by real-time reverse transcription polymerase chain reaction (real-time RT PCR). Data were statistically analyzed by unpaired t test.

Results: Compared to controls, GHRHKO mice, despite decreased TBW and N-A (P<0.0001), had significantly increased relative intra-abdominal (P<0.01) and subcutaneous (P<0.0001) fat, accompanied by significantly increased food intake per TBW (P<0.01) and unmodified TBW change. Adiponectin and visfatin mRNA levels were significantly decreased in both intra-abdominal (P<0.001) and subcutaneous fat (P<0.0001) of -/- mice. No significant difference in leptin mRNA levels was detected.

Conclusions: GHD due to targeted ablation of the GHRH gene in mice is associated with increased relative intra-abdominal and subcutaneous fat mass, a significant increase in food intake, and a decrease in adiponectin and visfatin gene expression in both fat depots.

[1] Alba M et al., Growth Horm IGF Res 2005; 15:275.

Nothing to Disclose: LB, RS, LR, CF, SL, AC, CD, AR, FM, GO, RS, MV

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

Sources of Research Support: Supported by Italian Ministry of Education grant