The goal of this proposal is to investigate the short and long-term effects of growth hormone (GH) on body composition and to investigate the hypothesis that intramyocellular lipid (IMCL) accumulation is a mechanism of insulin resistance in subjects with visceral obesity. Obesity is a strong independent risk factor for cardiovascular disease and type 2 diabetes. Visceral obesity has been shown to be associated with decreased secretion of GH compared to lean controls, and GH administration in obese patients reduces visceral fat and increases muscle mass. However, the physiology underlying the short and long-term effects of GH administration on glucose metabolism and insulin sensitivity are not well understood. Given the strong association between insulin resistance and cardiovascular disease, an understanding of the pathophysiology of GH induced changes on glucose metabolism and insulin resistance as well as body composition will be critical in the development of future strategies for enhancing GH efficacy without compromising insulin sensitivity. We hypothesize that IMCL are increased in obese subjects compared to lean controls, and IMCL correlate strongly with insulin resistance. In our first aim we will use 1H magnetic resonance spectroscopy (1H MRS) as a non-invasive technique to quantify IMCL in skeletal muscle in subjects with visceral obesity and lean controls and examine the relationship with detailed measures of insulin resistance and body composition. Our 2nd hypothesis is that short-term GH administration increases IMCL and insulin resistance. We will evaluate GH induced changes on IMCL and body composition after short-term (6 week) GH administration compared to placebo controls. We hypothesize that long-term GH administration decreases insulin resistance and increases lean mass with a decrease in visceral adipose tissue. In our third aim will evaluate GH induced changes on IMCL and body composition after long-term (6 month) GH administration and study the relationship of insulin resistance and change in body composition. This study will provide novel data on 1) the role and use of IMCL in determining glucose intolerance and 2) understanding of the pathophysiology of insulin resistance and altered body composition changes during short and long-term GH administration in visceral obesity. Ultimately, these data may reveal strategies to increase safety and efficacy of GH therapy.
| Dichtel, Laura E; Bjerre, Mette; Schorr, Melanie et al. (2018) The effect of growth hormone on bioactive IGF in overweight/obese women. Growth Horm IGF Res 40:20-27 |
| Schorr, Melanie; Dichtel, Laura E; Gerweck, Anu V et al. (2018) Sex differences in body composition and association with cardiometabolic risk. Biol Sex Differ 9:28 |
| Tabari, Azadeh; Torriani, Martin; Miller, Karen K et al. (2017) Anorexia Nervosa: Analysis of Trabecular Texture with CT. Radiology 283:178-185 |
| Dichtel, Laura E; Schorr, Melanie; Gill, Corey M et al. (2017) Body composition in pituitary, adrenal and iatrogenic Cushing's syndrome and effects of DHEAS levels. Clin Endocrinol (Oxf) 86:160-162 |
| Bachmann, Katherine N; Schorr, Melanie; Bruno, Alexander G et al. (2017) Vertebral Volumetric Bone Density and Strength Are Impaired in Women With Low-Weight and Atypical Anorexia Nervosa. J Clin Endocrinol Metab 102:57-68 |
| Bredella, Miriam A; Karastergiou, Kalypso; Bos, Stijn A et al. (2017) GH administration decreases subcutaneous abdominal adipocyte size in men with abdominal obesity. Growth Horm IGF Res 35:17-20 |
| Dichtel, Laura E; Corey, Kathleen E; Misdraji, Joseph et al. (2017) The Association Between IGF-1 Levels and the Histologic Severity of Nonalcoholic Fatty Liver Disease. Clin Transl Gastroenterol 8:e217 |
| Bachmann, Katherine N; Bruno, Alexander G; Bredella, Miriam A et al. (2016) Vertebral Strength and Estimated Fracture Risk Across the BMI Spectrum in Women. J Bone Miner Res 31:281-8 |
| Karastergiou, Kalypso; Bredella, Miriam A; Lee, Mi-Jeong et al. (2016) Growth hormone receptor expression in human gluteal versus abdominal subcutaneous adipose tissue: Association with body shape. Obesity (Silver Spring) 24:1090-1096 |
| Bove, Riley M; Gerweck, Anu V; Mancuso, Sarah M et al. (2016) Association between adiposity and cognitive function in young men: Hormonal mechanisms. Obesity (Silver Spring) 24:954-61 |
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