{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T15:27:34Z","timestamp":1759073254742},"reference-count":42,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"published-print":{"date-parts":[[2006,12]]},"abstract":"<jats:p>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\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup>) in combination with acipimox (GH + acipimox, 20 mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup>) or fenofibrate (GH + fenofibrate, 30 mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup>) 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.<\/jats:p>","DOI":"10.1152\/ajpendo.00614.2005","type":"journal-article","created":{"date-parts":[[2006,6,28]],"date-time":"2006-06-28T01:27:10Z","timestamp":1151458030000},"page":"E1212-E1219","source":"Crossref","is-referenced-by-count":9,"title":["Combination therapy with acipimox enhances the effect of growth hormone treatment on linear body growth in the normal and small-for-gestational-age rat"],"prefix":"10.1152","volume":"291","author":[{"given":"M. H.","family":"Vickers","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P. L.","family":"Hofman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P. D.","family":"Gluckman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P. E.","family":"Lobie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W. S.","family":"Cutfield","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-72-2-277"},{"key":"R2","doi-asserted-by":"crossref","unstructured":"Christie AW, McCormick DK, Emmison N, Kraemer FB, Alberti KG, and Yeaman SJ.Mechanism of anti-lipolytic action of acipimox in isolated rat adipocytes.Diabetologia39: 45\u201353, 1996.","DOI":"10.1007\/BF00400412"},{"key":"R3","doi-asserted-by":"crossref","unstructured":"Cordido F, Peino R, Penalva A, Alvarez CV, Casanueva FF, and Dieguez C.Impaired growth hormone secretion in obese subjects is partially reversed by acipimox-mediated plasma free fatty acid depression.J Clin Endocrinol Metab81: 914\u2013918, 1996.","DOI":"10.1210\/jcem.81.3.8772550"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1067\/mpd.2003.8"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)04055-6"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1210\/edrv-8-2-115"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.87.1.8293"},{"key":"R8","doi-asserted-by":"crossref","unstructured":"Fery F, Plat L, Baleriaux M, and Balasse EO.Inhibition of lipolysis stimulates whole body glucose production and disposal in normal postabsorptive subjects.J Clin Endocrinol Metab82: 825\u2013830, 1997.","DOI":"10.1210\/jc.82.3.825"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.84.12.6189"},{"key":"R10","doi-asserted-by":"crossref","unstructured":"Heptula RA, Boulware SD, Caprio S, Silver D, Sherwin RS, and Tambourlane WV.Decreased insulin sensitivity and compensatory hyperinsulinemia after hormone treatment in children with short stature.J Clin Endocrinol Metab82: 3234\u20133238, 1997.","DOI":"10.1210\/jc.82.10.3234"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1159\/000182188"},{"key":"R12","unstructured":"Hokken-Koelega AC, De Waal WJ, Sas TC, Van Pareren Y, and Arends NJ.Small for gestational age (SGA): endocrine and metabolic consequences and effects of growth hormone treatment.J Pediatr Endocrinol Metab17: 463\u2013469, 2004."},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1677\/jme.0.0220001"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-0515"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(97)70344-5"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.9.2331"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00124.2003"},{"key":"R18","doi-asserted-by":"crossref","unstructured":"Lee E, Nam S, Kim K, Lee H, Cho J, Nam M, Song Y, Lim S, and Huh K.Acipimox potentiates growth hormone (GH) response to GH-releasing hormone with or without pyridostigmine by lowering serum free fatty acid in normal and obese subjects.J Clin Endocrinol Metab80: 2495\u20132498, 1995.","DOI":"10.1210\/jcem.80.8.7629249"},{"key":"R19","doi-asserted-by":"crossref","unstructured":"Lewis RM, Vickers MH, Batchelor DC, Bassett NS, Johnston BM, and Skinner SJM.Effects of maternal captopril treatment on growth, blood glucose and plasma insulin in the fetal spontaneously hypertensive rat.Reprod Fertil Dev403\u2013408, 1999.","DOI":"10.1071\/RD99081"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M400601200"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1016\/S0026-0495(96)90288-7"},{"key":"R22","doi-asserted-by":"crossref","unstructured":"Moller J, Nielsen S, and Hansen TK.Growth hormone and fluid retention.Horm Res51: 116\u2013120, 1999.","DOI":"10.1159\/000053173"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1016\/S0026-0495(96)90029-3"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1016\/S1096-6374(02)00119-3"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.87.7.8597"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.1500779"},{"key":"R27","unstructured":"O'Neal DN, Kalfas A, Dunning PL, Christopher MJ, Sawyer SD, Ward GM, and Alford FP.The effect of 3 months of recombinant human growth hormone (GH) therapy on insulin and glucose-mediated glucose disposal and insulin secretion in GH-deficient adults: a minimal model analysis.J Clin Endocrinol Metab79: 975\u2013983, 1994."},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00444.2002"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1053\/j.semperi.2003.10.015"},{"key":"R30","doi-asserted-by":"crossref","unstructured":"Pontiroli A, Manzoni M, Malighetti M, and Lanzi R.Restoration of growth hormone (GH) response to GH-releasing hormone in elderly and obese subjects by acute pharmacological reduction of plasma free fatty acids.J Clin Endocrinol Metab81: 3998\u20134001, 1996.","DOI":"10.1210\/jcem.81.11.8923850"},{"key":"R31","unstructured":"Ranke MBand Lindberg A.Growth hormone treatment of short children born small for gestational age or with Silver-Russell syndrome: results from KIGS (Kabi International Growth Study), including the first report on final height.Acta Paediatr Suppl417: 18\u201326, 1996."},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198912283212605"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.48.9.1836"},{"key":"R34","doi-asserted-by":"crossref","unstructured":"Sas T, Mulder P, and Hokken-Koelega A.Body composition, blood pressure, and lipid metabolism before and during long-term growth hormone (GH) treatment in children with short stature born small for gestational age either with or without GH deficiency.J Clin Endocrinol Metab85: 3786\u20133792, 2000.","DOI":"10.1210\/jc.85.10.3786"},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.1490511"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.86.12.8096"},{"key":"R37","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.14.7239"},{"key":"R38","unstructured":"Vestergaard ET, Hansen TK, Nielsen S, Moller N, Christiansen JS, and Jorgensen JOL.Effects of GH replacement therpay in adults on serum levels of leptin and ghrelin: the role of lipolysis.Eur J Endocrinol154: 545\u2013549, 2005."},{"key":"R39","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.2000.279.1.E83"},{"key":"R40","doi-asserted-by":"publisher","DOI":"10.1210\/endo.142.9.8390"},{"key":"R41","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1750615"},{"key":"R42","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1500231"}],"container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpendo.00614.2005","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,7]],"date-time":"2023-05-07T21:16:15Z","timestamp":1683494175000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpendo.00614.2005"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,12]]},"references-count":42,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2006,12]]}},"alternative-id":["10.1152\/ajpendo.00614.2005"],"URL":"https:\/\/doi.org\/10.1152\/ajpendo.00614.2005","relation":{},"ISSN":["0193-1849","1522-1555"],"issn-type":[{"value":"0193-1849","type":"print"},{"value":"1522-1555","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,12]]}}}