National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
J Clin Endocrinol Metab. 2021 Sep 27;106(10):e4163-e4178. doi: 10.1210/clinem/dgab269.
Leptin is an adipokine that signals energy sufficiency. In rodents, leptin deficiency decreases energy expenditure (EE), which is corrected following leptin replacement. In humans, data are mixed regarding leptin-mediated effects on EE.
To determine the effects of metreleptin on EE in patients with lipodystrophy.
DESIGN, SETTING, AND PATIENTS: Nonrandomized crossover study of 25 patients with lipodystrophy (National Institutes of Health, 2013-2018).
The initiation cohort consisted of 17 patients without prior exposure to metreleptin, studied before and after 14 days of metreleptin. The withdrawal cohort consisted of 8 previously metreleptin-treated patients, studied before and after 14 days of metreleptin withdrawal.
24-h total energy expenditure (TEE), resting energy expenditure (REE), autonomic nervous system activity [heart rate variability (HrV)], plasma-free triiodothyronine (T3), free thyroxine (T4), epinephrine, norepinephrine, and dopamine.
In the initiation cohort, TEE and REE decreased by 5.0% (121 ± 152 kcal/day; P = 0.006) and 5.9% (120 ± 175 kcal/day; P = 0.02). Free T3 increased by 19.4% (40 ± 49 pg/dL; P = 0.01). No changes in catecholamines or HrV were observed. In the withdrawal cohort, free T3 decreased by 8.0% (P = 0.04), free T4 decreased by 11.9% (P = 0.002), and norepinephrine decreased by 34.2% (P = 0.03), but no changes in EE, epinephrine, dopamine, or HrV were observed.
Metreleptin initiation decreased EE in patients with lipodystrophy, but no changes were observed after metreleptin withdrawal. Thyroid hormone was higher on metreleptin in both initiation and withdrawal cohorts. Decreased EE after metreleptin in lipodystrophy may result from reductions in energy-requiring metabolic processes that counteract increases in EE via adipose tissue-specific neuroendocrine and adrenergic signaling.
瘦素是一种信号能量充足的脂肪因子。在啮齿动物中，瘦素缺乏会降低能量消耗（EE），而补充瘦素后可纠正这一情况。在人类中，关于瘦素对 EE 的介导作用的数据存在差异。
确定 metreleptin 对脂肪营养不良患者 EE 的影响。
设计、设置和患者：2013 年至 2018 年，对 25 例脂肪营养不良患者进行了非随机交叉研究（美国国立卫生研究院）。
起始队列由 17 例未接触过 metreleptin 的患者组成，在接受 metreleptin 治疗前和治疗后 14 天进行研究。停药队列由 8 例先前接受过 metreleptin 治疗的患者组成，在停药前和停药后 14 天进行研究。
24 小时总能量消耗（TEE）、静息能量消耗（REE）、自主神经系统活动[心率变异性（HrV）]、血浆游离三碘甲状腺原氨酸（T3）、游离甲状腺素（T4）、肾上腺素、去甲肾上腺素和多巴胺。
在起始队列中，TEE 和 REE 分别下降了 5.0%（121±152 千卡/天；P=0.006）和 5.9%（120±175 千卡/天；P=0.02）。游离 T3 增加了 19.4%（40±49 pg/dL；P=0.01）。未观察到儿茶酚胺或 HrV 的变化。在停药队列中，游离 T3 下降 8.0%（P=0.04），游离 T4 下降 11.9%（P=0.002），去甲肾上腺素下降 34.2%（P=0.03），但 EE、肾上腺素、多巴胺或 HrV 无变化。
Metreleptin 起始降低了脂肪营养不良患者的 EE，但停药后无变化。在起始和停药队列中，甲状腺激素在 metreleptin 上更高。脂肪营养不良患者使用 metreleptin 后 EE 降低可能是由于能量消耗代谢过程减少所致，这些过程通过脂肪组织特异性神经内分泌和肾上腺素能信号来对抗 EE 的增加。
