Leptin does not mediate short-term fasting-induced changes in growth hormone pulsatility but increases IGF-I in leptin deficiency states
Leptin does not mediate short-term fasting-induced changes in growth hormone pulsatility but increases IGF-I in leptin deficiency states
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DOI：
10.1210/jc.2008-0056
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发表时间：
2008-07-01
影响因子：
5.8
通讯作者：
Mantzoros, Christos S.
中科院分区：
文献类型：
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作者：
Chan, Jean L.;Williams, Catherine J.;Mantzoros, Christos S.
背景：急性和慢性能量缺乏状态的特征是GH分泌增加和IGF-I水平降低。目的：该研究的目的是确定在能量缺乏期间，瘦素水平的变化是否调节了GH-IGF系统。设计、设置、患者和干预：我们研究了14名健康的正常体重男性和女性在三种条件下：基线喂养和禁食72小时(诱导低血栓素血症)，给予安慰剂或重组甲硫基人瘦素(r-methuLeptin)(以逆转空腹相关的低脂血症)。结果：在短期能量缺乏期间，GH脉动性、紊乱程度和IGF结合蛋白(IGFBP)-1水平升高，而瘦素、胰岛素、IGF-I(总的和游离的)、IGFBP-4、IGFBP-6和GHBP的水平下降；r-MethuLeptin治疗可以抑制饥饿引起的IGF-I水平的下降。慢性能量缺乏组的总IGF-I、游离IGF-I、IGFBP-6和GHBP水平均低于正常对照组，r-metHuLeptin给药2周后对GH搏动性无明显影响，但在1个月后总IGF-I水平升高，并有升高游离IGF-I和IGFBP-3的趋势。结论：与能量缺乏相关的GH/IGF系统变化与瘦素缺乏无关。在急性能量缺乏时，替代剂量的r-metHuLeptin可拮抗饥饿引起的IGF-I的下降，而在慢性能量缺乏时，r-metHuLeptin使IGF-I升高，并有增加游离IGF-I和IGFBP-3的趋势。
Context: States of acute and chronic energy deficit are characterized by increased GH secretion and decreased IGF-I levels.Objective: The objective of the study was to determine whether changes in levels of leptin, a key mediator of the adaptation to starvation, regulate the GH-IGF system during energy deficit.Design, Setting, Patients, and Intervention: We studied 14 healthy normal-weight men and women during three conditions: baseline fed and 72-h fasting ( to induce hypoleptinemia) with administration of placebo or recombinant methionylhumanleptin (r-metHuLeptin) ( to reverse the fasting associated hypoleptinemia). We also studied eight normal-weight women with exercise-induced chronic energy deficit and hypothalamic amenorrhea at baseline and during 2-3 months of r-metHuLeptin treatment.Main Outcome Measures: GH pulsatility, IGF levels, IGF and GH binding protein (GHBP) levels were measured.Results: During short-term energy deficit, measures of GH pulsatility and disorderliness and levels of IGF binding protein (IGFBP)-1 increased, whereas leptin, insulin, IGF-I ( total and free), IGFBP-4, IGFBP-6, and GHBP decreased; r-metHuLeptin administration blunted the starvation-associated decrease of IGF-I. In chronic energy deficit, total and free IGF-I, IGFBP-6, and GHBP levels were lower, compared with euleptinemic controls; r-metHuLeptin administration had no major effect on GH pulsatility after 2 wk but increased total IGF-I levels and tended to increase free IGF-I and IGFBP-3 after 1 month.Conclusions: The GH/IGF system changes associated with energy deficit are largely independent of leptin deficiency. During acute energy deficit, r-metHuLeptin administration in replacement doses blunts the starvation- induced decrease of IGF-I, but during chronic energy deficit, r-metHuLeptin administration increases IGF-I and tends to increase free IGF-I and IGFBP-3.