Abstract：
Seipin is a key regulator of lipid metabolism, the deficiency of which leads to severe lipodystrophy. Hypothalamus is the pivotal center of brain that modulates appetite and energy homeostasis, where Seipin is abundantly expressed. Whether and how Seipin deficiency leads to systemic metabolic disorders via hypothalamus-involved energy metabolism dysregulation remains to be elucidated. In the present study, we demonstrated that Seipin-deficiency induced hypothalamic inflammation, reduction of anorexigenic pro-opiomelanocortin (POMC), and elevation of orexigenic agonist-related peptide (AgRP). Importantly, administration of rosiglitazone, a thiazolidinedione antidiabetic agent, rescued POMC and AgRP expression, suppressed hypothalamic inflammation, and restored energy homeostasis in Seipin knockout mice. Our findings offer crucial insights into the mechanism of Seipin deficiency-associated energy imbalance and indicates that rosiglitazone could serve as potential intervening agent towards metabolic disorders linked to Seipin.
摘要：
Seipin是脂质代谢的关键调节剂，其缺乏导致严重的脂肪营养不良。下丘脑是大脑调节食欲和能量稳态的关键中心，Seipin被大量表达。Seipin缺乏是否以及如何通过下丘脑参与的能量代谢失调导致全身代谢紊乱仍有待阐明。在本研究中,我们证明了Seipin缺乏引起下丘脑炎症，减少厌食性前阿片黑皮质素（POMC），和促食欲激动剂相关肽（AgRP）的升高。重要的是,罗格列酮的给药，噻唑烷二酮抗糖尿病药，拯救POMC和AgRP表达，抑制下丘脑炎症，并恢复Seipin基因敲除小鼠的能量稳态。我们的发现为Seipin缺乏相关能量失衡的机制提供了重要的见解，并表明罗格列酮可以作为与Seipin相关的代谢紊乱的潜在干预剂。
