瘦素会急剧增加脂肪营养不良患者的肝脏甘油三酯分泌。

IF 10.8 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Metabolism: clinical and experimental Pub Date : 2025-04-07 DOI:10.1016/j.metabol.2025.156261

Marianna Beghini , Matthäus Metz , Clemens Baumgartner , Peter Wolf , Magdalena Bastian , Martina Hackl , Sabina Baumgartner-Parzer , Rodrig Marculescu , Michael Krebs , Jürgen Harreiter , Stephanie Brandt , Konstanze Miehle , Giovanni Ceccarini , Silvia Magno , Caterina Pelosini , Christel Tran , Alessandra Gambineri , Carolina Cecchetti , Liliana-Imi Gard , Robert Risti , Thomas Scherer

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引用次数: 0

摘要

背景和目的：美曲瘦素改善肝脏脂肪变性部分独立于其厌食作用。我们之前的研究表明，美曲瘦素增加了啮齿类动物和需要完整肝脏自主神经支配的健康人肝脏极低密度脂蛋白甘油三酯（VLDL1-TG）的输出。本研究的主要目的是研究美曲瘦素是否通过增加VLDL1-TG的输出而在脂肪营养不良患者中具有抗脂肪变性的特性。此外，我们提出了一个在肝移植后接受美曲瘦素治疗的全身性脂肪营养不良的病例，这是一个肝脏自主神经去神经的模型。方法：在这项随机、安慰剂对照、交叉试验（EudraCT 2017-003014-22）中，我们评估了10例患者(8名女性，2名男性；平均年龄 ± SD: 49 ± 14 岁；（9)家族性部分和(1)全身性脂肪营养不良）对肝脏VLDL1-TG分泌和肝细胞脂质含量（HCL）的影响，分别通过静脉脂肪乳试验和1h磁共振波谱测定。结果：我们发现单次注射美曲瘦素使肝脏VLDL1-TG分泌增加75 %(平均差 ± SD: +219 ± 149 mg/h美曲瘦素与安慰剂相比； = 0.001页),没有重大变化在盐酸3 h(平均差 ± SD: 8 ± 14 % metreleptin与安慰剂,p = 0.14)。肝移植后全身性脂肪营养不良患者的美曲瘦素治疗未能改善肝脂肪变性，尽管改善了葡萄糖和脂质代谢。结论：瘦素可急剧增加脂肪营养不良患者肝脏VLDL1-TG分泌，可能与美曲瘦素的体重无关的抗脂肪变性作用有关。病例报告表明，完整的自主肝神经支配可能需要这种作用，值得进一步研究。

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Leptin acutely increases hepatic triglyceride secretion in patients with lipodystrophy

Background and aims

Metreleptin ameliorates hepatic steatosis partially independent of its anorexic action. We previously showed that metreleptin increases hepatic very low-density lipoprotein triglycerides (VLDL1-TG) export in rodents and healthy humans requiring intact hepatic autonomic innervation. The primary aim of this study was to investigate whether metreleptin has anti-steatotic properties in patients with lipodystrophy by increasing VLDL1-TG export. In addition, we present a case of generalized lipodystrophy undergoing metreleptin treatment after liver transplantation, a model for hepatic autonomic denervation.

Methods

In this randomized, placebo-controlled, crossover trial (EudraCT 2017-003014-22) we assessed the acute effects of a single metreleptin injection in 10 patients (8 females, 2 males; mean age ± SD: 49 ± 14 yrs; 9 familial partial and 1 generalized lipodystrophy) on hepatic VLDL1-TG secretion and hepatocellular lipid content (HCL) measured via an intravenous fat emulsion test and ¹H-magnetic resonance spectroscopy, respectively.

Results

We found that a single injection of metreleptin increased hepatic VLDL1-TG secretion by 75 % (mean difference ± SD: +219 ± 149 mg/h metreleptin vs. placebo; p = 0.001), without significant changes in HCL within 3 h (mean difference ± SD: −8 ± 14 % metreleptin vs. placebo, p = 0.14). Metreleptin therapy in a patient with generalized lipodystrophy following liver transplantation failed to ameliorate hepatic steatosis despite improving glucose and lipid metabolism.

Conclusions

Leptin acutely increases hepatic VLDL1-TG secretion in patients with lipodystrophy, likely contributing to metreleptin's body weight-independent anti-steatotic effects. The case report suggests that intact autonomic liver innervation may be required for this action, warranting further research.

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来源期刊

Metabolism: clinical and experimental 医学-内分泌学与代谢

CiteScore

18.90

自引率

3.10%

发文量

310

审稿时长

16 days

期刊介绍： Metabolism upholds research excellence by disseminating high-quality original research, reviews, editorials, and commentaries covering all facets of human metabolism. Consideration for publication in Metabolism extends to studies in humans, animal, and cellular models, with a particular emphasis on work demonstrating strong translational potential. The journal addresses a range of topics, including: - Energy Expenditure and Obesity - Metabolic Syndrome, Prediabetes, and Diabetes - Nutrition, Exercise, and the Environment - Genetics and Genomics, Proteomics, and Metabolomics - Carbohydrate, Lipid, and Protein Metabolism - Endocrinology and Hypertension - Mineral and Bone Metabolism - Cardiovascular Diseases and Malignancies - Inflammation in metabolism and immunometabolism