Combination therapy with acipimox enhances the effect of growth hormone treatment on linear body growth in the normal and small-for-gestational-age rat

• Published in: American journal of physiology: endocrinology and metabolism Vol. 291; no. 6; pp. E1212 - E1219
• Main Authors: Vickers, M. H, Hofman, P. L, Gluckman, P. D, Lobie, P. E, Cutfield, W. S
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.12.2006
• Subjects: Animals; Birth Weight - physiology; Blood Pressure - drug effects; Bone Development - drug effects; Fatty acids; Fatty Acids, Nonesterified - blood; Female; Fenofibrate - pharmacology; Growth - drug effects; Growth Hormone - pharmacology; Growth hormones; Hematocrit; Hypolipidemic Agents - pharmacology; Insulin - blood; Insulin-Like Growth Factor I - metabolism; Liver - drug effects; Liver - growth & development; Male; Medical treatment; Organ Size - drug effects; Pregnancy; Pyrazines - pharmacology; Rats; Rats, Wistar; Rodents; Side effects; Studies; Tibia - drug effects; Tibia - growth & development; Weight Gain - drug effects
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00614.2005

Liggins Institute and National Research Centre for Growth and Development, University of Auckland, Auckland, New Zealand Submitted 5 December 2005 ; accepted in final form 14 June 2006 Growth hormone (GH) therapy is often associated with adverse side effects, including impaired insulin sensitivity. GH treatment of children with idiopathic short stature does not lead to an optimized final adult height. It has been demonstrated that FFA reduction induced by pharmacological antilipolysis can stimulate GH secretion per se in both normal subjects and those with GH deficiency. However, to date, no investigation has been undertaken to establish efficacy of combination treatment with GH and FFA regulators on linear body growth. Using a model of maternal undernutrition in the rat to induce growth-restricted offspring, we investigated the hypothesis that combination treatment with GH and FFA regulators can enhance linear body growth above that of GH alone. At postnatal day 28 , male offspring of normally nourished mothers (controls) and offspring born with low birth weight [small for gestational age (SGA)] were treated with saline, GH, or GH (5 mg·kg –1 ·day –1 ) in combination with acipimox (GH + acipimox, 20 mg·kg –1 ·day –1 ) or fenofibrate (GH + fenofibrate, 30 mg·kg –1 ·day –1 ) for 40 days. GH plus acipimox treatment significantly enhanced linear body growth in the control and SGA animals above that of GH, as quantified by tibial and total body length. Treatment with GH significantly increased fasting plasma insulin, insulin-to-glucose ratio, and plasma volumes in control and SGA animals but was not significantly different between saline and GH-plus-acipimox-treated animals. GH-induced lipolysis was blocked by GH plus acipimox treatment in both control and SGA animals, concomitant with a significant reduction in fasting plasma FFA and insulin concentrations. This is the first study to show that GH plus acipimox combination therapy, via pharmacological blocking of lipolysis during GH exposure, can significantly enhance the efficacy of GH in linear growth promotion and ameliorate unwanted metabolic side effects. growth hormone; acipimox; insulin; free fatty acids Address for reprint requests and other correspondence: M. Vickers, Liggins Institute, Faculty of Medical and Health Sciences, Univ. of Auckland, Auckland, New Zealand, (e-mail: m.vickers{at}auckland.ac.nz )