Najjar Sonia M, Abdolahipour Raziyeh, Ghadieh Hilda E, Jahromi Marziyeh Salehi, Najjar John A, Abuamreh Basil A M, Zaidi Sobia, Kumarasamy Sivarajan, Muturi Harrison T
Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA.
Diabetes Institute, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA.
Biomedicines. 2022 Aug 5;10(8):1899. doi: 10.3390/biomedicines10081899.
Insulin stores lipid in adipocytes and prevents lipolysis and the release of non-esterified fatty acids (NEFA). Excessive release of NEFA during sustained energy supply and increase in abdominal adiposity trigger systemic insulin resistance, including in the liver, a major site of insulin clearance. This causes a reduction in insulin clearance as a compensatory mechanism to insulin resistance in obesity. On the other hand, reduced insulin clearance in the liver can cause chronic hyperinsulinemia, followed by downregulation of insulin receptor and insulin resistance. Delineating the cause-effect relationship between reduced insulin clearance and insulin resistance has been complicated by the fact that insulin action and clearance are mechanistically linked to insulin binding to its receptors. This review discusses how NEFA mobilization contributes to the reciprocal relationship between insulin resistance and reduced hepatic insulin clearance, and how this may be implicated in the pathogenesis of non-alcoholic fatty liver disease.
胰岛素将脂质储存于脂肪细胞中，并阻止脂肪分解以及非酯化脂肪酸（NEFA）的释放。在持续能量供应期间NEFA的过度释放以及腹部肥胖的增加会引发全身性胰岛素抵抗，包括在肝脏这一胰岛素清除的主要部位。这会导致胰岛素清除减少，作为肥胖中胰岛素抵抗的一种代偿机制。另一方面，肝脏中胰岛素清除的减少会导致慢性高胰岛素血症，随后胰岛素受体下调以及胰岛素抵抗。由于胰岛素作用和清除在机制上与胰岛素与其受体的结合相关联，因此明确胰岛素清除减少与胰岛素抵抗之间的因果关系变得复杂。本综述讨论了NEFA动员如何促成胰岛素抵抗与肝脏胰岛素清除减少之间的相互关系，以及这可能如何与非酒精性脂肪性肝病的发病机制相关。
