Akinci Baris, Ajluni Nevin, Meral Rasimcan, Neidert Adam Hugh, Freitas Maria Foss, Gilio Donatella, Conjeevaram Hari, Oral Elif Arioglu
Caswell Diabetes Institute and Division of Metabolism, Endocrinology & Diabetes, University of Michigan, Ann Arbor, MI 48109, USA.
Technological Research Program, Izmir Biomedicine and Genome Center & Depark, Dokuz Eylul University Health Campus, 35330 Izmir, Turkey.
J Endocr Soc. 2025 May 7;9(8):bvaf067. doi: 10.1210/jendso/bvaf067. eCollection 2025 Aug.
Partial lipodystrophy (PL) is a rare disease characterized by selective loss of subcutaneous fat.
To evaluate changes in apolipoproteins, hepatokines, hormones, appetite regulators, and inflammatory markers in patients with PL treated with leptin, assess postprandial metabolism and 24-hour dynamics, and identify predictors of hepatic and metabolic response to therapy.
We studied 19 subjects from our previous clinical study (NCT01679197), which investigated the effect of leptin on metabolic dysfunction-associated steatohepatitis associated with PL. A mixed-meal test was performed in a subgroup of 14 patients, and paired 24-hour frequent sampling with standardized meals was completed in 5 individuals.
Leptin treatment led to reductions in apolipoproteins B, CII, CIII, and E ( < .05). Levels of ANGPTL3 tended to decrease after leptin treatment ( = .079). The mixed-meal test revealed significant reductions in triglyceride area under the curve ( = .017) and glucose excursions at several postmeal time points ( < .05). The immediate GIP secretion in response to a meal attenuated after leptin therapy ( = .005 at 60 minutes). Ghrelin levels showed an increase after leptin administration. The response to leptin treatment was associated with several factors, including baseline carbohydrate intake, leptin and triglyceride levels and triglyceride-rich apolipoproteins, and changes in triglyceride-rich apolipoproteins ( < .05 for all). Changes in IGF-1 levels were correlated with improvements in metabolic and liver parameters ( < .05).
Leptin therapy modulates lipid metabolism, postprandial glucose regulation, and appetite signaling in patients with PL, with responses associated with metabolic parameters and carbohydrate intake.
部分脂肪营养不良（PL）是一种罕见疾病，其特征为皮下脂肪选择性丢失。
评估接受瘦素治疗的PL患者载脂蛋白、肝因子、激素、食欲调节因子和炎症标志物的变化，评估餐后代谢和24小时动态变化，并确定肝脏和代谢对治疗反应的预测因素。
我们研究了来自我们之前临床研究（NCT01679197）的19名受试者，该研究调查了瘦素对与PL相关的代谢功能障碍相关脂肪性肝炎的影响。对14名患者的亚组进行了混合餐试验，并对5名个体完成了标准化餐食的24小时配对频繁采样。
瘦素治疗导致载脂蛋白B、CII、CIII和E减少（P<0.05）。瘦素治疗后血管生成素样蛋白3（ANGPTL3）水平趋于下降（P = 0.079）。混合餐试验显示曲线下甘油三酯面积显著减少（P = 0.017），以及餐后几个时间点的血糖波动（P<0.05）。瘦素治疗后，进食后立即分泌的葡萄糖依赖性促胰岛素多肽（GIP）减弱（60分钟时P = 0.005）。瘦素给药后胃饥饿素水平升高。对瘦素治疗的反应与几个因素相关，包括基线碳水化合物摄入量、瘦素和甘油三酯水平以及富含甘油三酯的载脂蛋白，以及富含甘油三酯的载脂蛋白的变化（所有P<0.05）。胰岛素样生长因子-1（IGF-1）水平的变化与代谢和肝脏参数的改善相关（P<0.05）。
瘦素治疗可调节PL患者的脂质代谢、餐后血糖调节和食欲信号传导，其反应与代谢参数和碳水化合物摄入量相关。
