PDF(Pubmed)
Abstract：
Leptin regulates lipid metabolism, maximizing insulin sensitivity; however, peripheral leptin resistance is not fully understood, and its contribution to metabolic dysfunction-associated steatotic liver disease (MASLD) is unclear. This study evaluated the contribution of the leptin axis to MASLD in humans. Forty-three participants, mostly female (86.04%), who underwent cholecystectomy were biopsied. Of the participants, 24 were healthy controls, 8 had MASLD, and 11 had metabolic dysfunction-associated steatohepatitis (MASH). Clinical and biochemical data and the gene expression of leptin, leptin receptor (LEPR), suppressor of cytokine signaling 3 (SOCS3), sterol regulatory element-binding transcription factor 1 (SREBF1), stearoyl-CoA desaturase-1 (SCD1), and patatin-like phospholipase domain-containing protein 2 (PNPLA2), were determined from liver and adipose tissue. Higher serum leptin and LEPR levels in the omental adipose tissue (OAT) and liver with MASH were found. In the liver, LEPR was positively correlated with leptin expression in adipose tissue, and SOCS3 was correlated with SREBF1-SCD1. In OAT, SOCS3 was correlated with insulin resistance and transaminase enzymes (p < 0.05 for all. In conclusion, we evidenced the correlation between the peripheral leptin resistance axis in OAT-liver crosstalk and the complications of MASLD in humans.
摘要：
瘦素调节脂质代谢，最大化胰岛素敏感性；然而，外周瘦素抵抗尚未完全了解，其对代谢功能障碍相关脂肪变性肝病（MASLD）的贡献尚不清楚。这项研究评估了瘦素轴对人类MASLD的贡献。43名与会者，主要是女性(86.04%)，接受胆囊切除术的患者进行了活检。在参与者中，24个是健康对照，8有体格，11人患有代谢功能障碍相关脂肪性肝炎（MASH）。临床和生化数据和瘦素的基因表达，瘦素受体(LEPR),细胞因子信号抑制因子3（SOCS3），甾醇调节元件结合转录因子1(SREBF1),硬脂酰辅酶A去饱和酶-1（SCD1），和patatatin样磷脂酶结构域含蛋白2（PNPLA2），从肝脏和脂肪组织中确定。在MASH的网膜脂肪组织（OAT）和肝脏中发现较高的血清瘦素和LEPR水平。在肝脏中，LEPR与瘦素在脂肪组织中的表达呈正相关,SOCS3与SREBF1-SCD1相关。在OAT,SOCS3与胰岛素抵抗和转氨酶相关（均p<0.05。总之,我们证明了OAT-肝脏串扰中外周瘦素抵抗轴与人类MASLD并发症之间的相关性。
