Lustig R H, Sen S, Soberman J E, Velasquez-Mieyer P A
Department of Pediatrics, University of California, San Francisco, CA 94143-0434, USA.
Int J Obes Relat Metab Disord. 2004 Oct;28(10):1344-8. doi: 10.1038/sj.ijo.0802753.
Leptin resistance is a hallmark of obesity, but its etiology is unknown, and its clinical measurement is elusive. Leptin-sensitive subjects have normal resting energy expenditure (REE) at a low leptin concentration, while leptin-resistant subjects have a normal REE at a higher leptin concentration; thus, the ratio of REE:Leptin may provide a surrogate index of leptin sensitivity. We examined changes in REE and leptin in a cohort of 17 obese subjects during experimental weight loss therapy with the insulin-suppressive agent octreotide-LAR, 40 mg i.m. q28d for 6 months. Six subjects lost significant weight (>10%) and BMI (>-3 kg/m(2)) with a 34% decline in leptin and a 46% decrease in insulin area under the curve (IAUC) to oral glucose tolerance testing. These subjects maintained their pretreatment REE, and thus exhibited a rise in REE:Leptin, while the other 11 showed minimal changes in each of these parameters. For the entire cohort, the change in IAUC correlated negatively with the change in REE:Leptin. These results suggest that the REE:Leptin ratio, while derivative, may serve as a useful clinical indicator of changes in leptin sensitivity within obese subjects. They also support the possibilities that hyperinsulinemia may be a proximate cause of leptin resistance, and that reduction of insulinemia may promote weight loss by improving leptin sensitivity.
瘦素抵抗是肥胖的一个标志，但其病因尚不清楚，临床测量也难以捉摸。瘦素敏感的受试者在低瘦素浓度下静息能量消耗（REE）正常，而瘦素抵抗的受试者在较高瘦素浓度下REE正常；因此，REE与瘦素的比值可能提供瘦素敏感性的替代指标。我们在一组17名肥胖受试者中进行了实验性减肥治疗，使用胰岛素抑制药物长效奥曲肽，40mg肌肉注射，每28天一次，共6个月，观察了REE和瘦素的变化。6名受试者体重显著下降（>10%）且体重指数（>-3kg/m²），瘦素下降34%，口服葡萄糖耐量试验的胰岛素曲线下面积（IAUC）下降46%。这些受试者维持了治疗前的REE，因此REE与瘦素的比值升高，而其他11名受试者在这些参数上变化极小。对于整个队列，IAUC的变化与REE与瘦素比值的变化呈负相关。这些结果表明，REE与瘦素的比值虽然是派生的，但可能是肥胖受试者瘦素敏感性变化的有用临床指标。它们还支持高胰岛素血症可能是瘦素抵抗的直接原因，以及降低胰岛素血症可能通过改善瘦素敏感性促进体重减轻的可能性。
