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

Polyxeni Koutkia, Gary Meininger, Bridget Canavan, Jeff Breu, Steven Grinspoon
2004 American Journal of Physiology. Endocrinology and Metabolism  
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 HIVlipodystrophy. 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
more » ... lar 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 hormonereleasing 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 Ϯ 0.6, 4.7 Ϯ 0.8, and 4.5 Ϯ 0.3 pulses/12 h in the HIV-lipodystrophic, HIV-nonlipodystrophic, and healthy control groups, respectively, P Ͼ 0.05) but markedly reduced GH secretion pulse area (1.14 Ϯ 0.27 vs. 4.67 Ϯ 1.24 ng⅐ml Ϫ1 ⅐min, P Ͻ 0.05, HIV-lipodystrophic vs. HIV-nonlipodystrophic; 1.14 Ϯ 0.27 vs. 3.18 Ϯ 0.92 ng⅐ml Ϫ1 ⅐min, P Ͻ 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 Ϯ 46 vs. 514 Ϯ 37 pg/ml, P Ͻ 0.05, HIV-lipodystrophic vs. HIV-nonlipodystrophic; 418 Ϯ 46 vs. 546 Ϯ 45 pg/ml, P Ͻ 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 THE PHYSIOLOGICAL REGULATION of growth hormone (GH) is complex and occurs under the dual influence of growth hormone-releasing hormone (GHRH) and somatostatin. More recently, it has been suggested that ghrelin, a nutritionally mediated gut peptide and GH secretagogue (19), may also be an important regulator of GH secretion. GH is reduced in generalized obesity (35), and recent studies suggest that visceral fat is a critical determinant of GH secretion (6). Increased somatostatin tone is thought to contribute to reduced GH secretion in obesity, but little is known regarding the pattern of GH
doi:10.1152/ajpendo.00335.2003 pmid:14559725 fatcat:rvevoo6vd5gm3iwitzmu7l66cy