Roberts G A, Holt R I, Ghatei M A, Baker A J, Bloom S R, Miell J P
Department of Medicine, King's College School of Medicine and Dentistry, London, UK.
Clin Endocrinol (Oxf). 1998 Apr;48(4):401-6. doi: 10.1046/j.1365-2265.1998.00448.x.
Leptin, the product of the ob gene, is a postulated feedback regulator of adiposity with appetite suppressant and catabolic effects. Catabolic states are associated with decreased body fat mass as a result of both nutritional and metabolic perturbation. Low serum leptin has been described previously in a number of catabolic states. It has been unclear whether the observed changes in leptin are a cause or consequence of changes in adiposity. Paediatric end-stage liver disease (ESLD) is characterized by decreased body fat mass and poor linear growth. Successful treatment by orthotopic liver transplantation (OLT) is accompanied by increase in fat mass. We investigated the hypothesis that serum leptin would be low in paediatric ESLD and that increase in body fat mass post-OLT would result in increased serum leptin.
Serum leptin and insulin were measured by radioimmunoassay in children with ESLD before and after successful OLT and in age-matched controls.
Twenty-four children with ESLD attending the outpatient department of King's College Hospital, London and 10 age-matched controls.
Anthropometric measurements were performed according to standard techniques and standard deviation (SDS) derived from population standards. Serum leptin and insulin were measured by radioimmunoassay.
Serum leptin pre-OLT, leptin (4.06 micrograms/l, [3.45, 5.68] median, with 25th and 75th interquartile ranges) was significantly lower than controls (6.62 micrograms/l, [4.33, 8.05], P = 0.02). Following OLT, serum leptin fell to levels which were significantly lower than pre-OLT values (3.32 micrograms/l, [2.30, 3.99], P = 0.01). There was no significant difference between boys and girls either pre-OLT (boys; 3.64 micrograms/l, [2.45, 5.57], girls; 4.14 micrograms/l, [3.18, 5.65]) or post-OLT (boys; 3.32 micrograms/l, [2.93, 3.62], girls; 3.69 micrograms/l, [2.23, 4.63]. Neither the age at OLT nor the age at the time of blood sampling was correlated with serum leptin pre-OLT or post-OLT. Pre-OLT the children were significantly malnourished with low measures of body fat mass (mid-arm circumference (MAC) SDS -1.90 [-4.67, -1.07]; triceps skinfold thickness (TSF) SDS -1.53, [-2.23, -0.23]; body mass index (BMI) 16.2, [15.5, 16.9]). Three months post-OLT, there were significant improvements in MAC SDS (-0.77, [-1.08, -0.20], P = 0.02) and TSF SDS (-0.41, [-1.95, -0.38], P = 0.003), but no significant change in BMI (15.9 [15.3, 16.7], P = 0.41. Pre-OLT, log serum leptin did not correlate with BMI, MAC SDS or TSF SDS. In contrast, post-OLT, there was a positive correlation between log serum leptin and BMI (r = 0.59, P = 0.003), MAC SDS (r = 0.49, P = 0.01) and TSF SDS (r = 0.41, P = 0.05). BMI also correlated with log serum leptin in the control children (r = 0.64, P = 0.04).
Serum leptin is low in children with end-stage liver disease but does not show the expected correlation with measures of body fat mass. Surprisingly, following orthotopic liver transplantation serum leptin falls significantly despite significant increases in measures of body fat mass (triceps skinfold thickness standard deviation scores, mid-arm circumference standard deviation scores). Orthotopic liver transplantation restores the expected correlation of serum leptin with measures of body fat mass within the treatment group. The elevation of serum leptin above predicted levels in paediatric end-stage liver disease offers a mechanism for the anorexia and cachexia characteristic of this disease.
瘦素是ob基因的产物，被认为是一种肥胖的反馈调节因子，具有抑制食欲和分解代谢的作用。分解代谢状态与因营养和代谢紊乱导致的体脂量减少有关。先前在多种分解代谢状态下均有血清瘦素水平降低的描述。目前尚不清楚所观察到的瘦素变化是肥胖改变的原因还是结果。小儿终末期肝病（ESLD）的特征是体脂量减少和线性生长不良。原位肝移植（OLT）成功治疗后会伴随体脂量增加。我们研究了以下假设：小儿ESLD患者血清瘦素水平会降低，OLT术后体脂量增加会导致血清瘦素水平升高。
采用放射免疫分析法测定成功接受OLT的小儿ESLD患者术前和术后以及年龄匹配对照组儿童的血清瘦素和胰岛素水平。
伦敦国王学院医院门诊的24例小儿ESLD患者和10例年龄匹配的对照组儿童。
根据标准技术进行人体测量，并根据人群标准得出标准差（SDS）。采用放射免疫分析法测定血清瘦素和胰岛素水平。
OLT术前血清瘦素水平为4.06微克/升（中位数[3.45, 5.68]，第25和第75四分位数间距），显著低于对照组（6.62微克/升，[4.33, 8.05]，P = 0.02）。OLT术后，血清瘦素水平降至显著低于术前值的水平（3.32微克/升，[2.30, 3.99]，P = 0.01）。术前男孩和女孩之间无显著差异（男孩：3.64微克/升，[2.45, 5.57]，女孩：4.14微克/升，[3.18, 5.65]），术后也无显著差异（男孩：3.32微克/升，[2.93, 3.62]，女孩：3.69微克/升，[2.23, 4.63]）。OLT时的年龄和采血时的年龄与OLT术前或术后血清瘦素均无相关性。术前患儿存在明显营养不良，体脂量测量值较低（上臂中部周长（MAC）SDS -1.90 [-4.67, -1.07]；三头肌皮褶厚度（TSF）SDS -1.53，[-2.23, -0.23]；体重指数（BMI）16.2，[15.5, 16.9]）。OLT术后3个月，MAC SDS（-0.77，[-1.08, -0.20]，P = 0.02）和TSF SDS（-0.41，[-1.95, -0.38]，P = 0.003）有显著改善，但BMI无显著变化（15.9 [15.3, 16.7]，P = 0.41）。术前，血清瘦素对数与BMI、MAC SDS或TSF SDS均无相关性。相比之下，OLT术后，血清瘦素对数与BMI（r = 0.59，P = 0.003）、MAC SDS（r = 0.49, P = 0.01）和TSF SDS（r = 0.41, P = 0.05）呈正相关。对照组儿童的BMI与血清瘦素对数也呈正相关（r = 0.64, P = 0.04）。
终末期肝病患儿血清瘦素水平较低，但与体脂量测量值未显示出预期的相关性。令人惊讶的是，原位肝移植术后尽管体脂量测量值（三头肌皮褶厚度标准差评分、上臂中部周长标准差评分）显著增加，但血清瘦素却显著下降。原位肝移植在治疗组中恢复了血清瘦素与体脂量测量值之间的预期相关性。小儿终末期肝病患者血清瘦素高于预测水平为该病特征性的厌食和恶病质提供了一种机制。
