Metabolic regulation of growth hormone by free fatty acids, somatostatin, and ghrelin in HIV-lipodystrophy

• Published in: American journal of physiology: endocrinology and metabolism Vol. 286; no. 2; pp. E296 - E303
• Main Authors: Koutkia, Polyxeni, Meininger, Gary, Canavan, Bridget, Breu, Jeff, Grinspoon, Steven
• Format: Journal Article
• Language: English
• Published: United States 01.02.2004
• Subjects: Adult; Algorithms; Case-Control Studies; Fatty Acids, Nonesterified - blood; Ghrelin; HIV-Associated Lipodystrophy Syndrome - blood; HIV-Associated Lipodystrophy Syndrome - drug therapy; Human Growth Hormone - blood; Human Growth Hormone - secretion; Humans; Hypolipidemic Agents - therapeutic use; Insulin-Like Growth Factor I - metabolism; Male; Peptide Hormones - blood; Pyrazines - therapeutic use; Somatostatin - blood
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00335.2003

1 Program in Nutritional Metabolism and Neuroendocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston 02114; and 2 General Clinical Research Center, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 Submitted 18 July 2003 ; accepted in final form 9 October 2003 Human immunodeficiency virus (HIV)-lipodystrophy is a syndrome characterized by changes in fat distribution and insulin resistance. Prior studies suggest markedly reduced growth hormone (GH) levels in association with excess visceral adiposity among patients with HIV-lipodystrophy. We investigated mechanisms of altered GH secretion in a population of 13 male HIV-infected patients with evidence of fat redistribution, compared with 10 HIV-nonlipodystrophic patients and 11 male healthy controls similar in age and body mass index (BMI). Although similar in BMI, the lipodystrophic group was characterized by increased visceral adiposity, free fatty acids (FFA), and insulin and reduced extremity fat. We investigated ghrelin and the effects of acute lowering of FFA by acipimox on GH responses to growth hormone-releasing hormone (GHRH). We also investigated somatostatin tone, comparing GH response to combined GHRH and arginine vs. GHRH alone with a subtraction algorithm. Our data demonstrate an equivalent number of GH pulses (4.1 ± 0.6, 4.7 ± 0.8, and 4.5 ± 0.3 pulses/12 h in the HIV-lipodystrophic, HIV-nonlipodystrophic, and healthy control groups, respectively, P > 0.05) but markedly reduced GH secretion pulse area (1.14 ± 0.27 vs. 4.67 ± 1.24 ng·ml –1 ·min, P < 0.05, HIV-lipodystrophic vs. HIV-nonlipodystrophic; 1.14 ± 0.27 vs. 3.18 ± 0.92 ng·ml –1 ·min, P < 0.05 HIV-lipodystrophic vs. control), GH pulse area, and GH pulse width in the HIV-lipodystrophy patients compared with the control groups. Reduced ghrelin (418 ± 46 vs. 514 ± 37 pg/ml, P < 0.05, HIV-lipodystrophic vs. HIV-nonlipodystrophic; 418 ± 46 vs. 546 ± 45 pg/ml, P < 0.05, HIV-lipodystrophic vs. control), impaired GH response to GHRH by excess FFA, and increased somatostatin tone contribute to reduced GH secretion in patients with HIV-lipodystrophy. These data provide novel insight into the metabolic regulation of GH secretion in subjects with HIV-lipodystrophy. growth hormone-releasing hormone; human immunodeficiency virus Address for reprint requests and other correspondence: S. Grinspoon, Program in Nutritional Metabolism, LON 207, Massachusetts General Hospital, 55 Fruit St., Boston, MA 02114 (E-mail: sgrinspoon{at}partners.org ).