Pennington Biomedical Research Center, Baton Rouge, Louisiana.
Am J Physiol Endocrinol Metab. 2020 Jan 1;318(1):E11-E21. doi: 10.1152/ajpendo.00309.2019. Epub 2019 Oct 29.
There are endocrine and immunological changes that occur during onset and progression of the overweight and obese states. The inhibitor of nuclear factor-κB kinase-ε (IKKε) was originally described as an inducible protein kinase; whole body gene deletion or systemic pharmaceutical targeting of this kinase improved insulin sensitivity and glucose tolerance in mice. To investigate the primary sites of action associated with IKKε during weight gain, we describe the first mouse line with conditional elimination of IKKε in the liver (IKKε). IKKε mice and littermate controls gain weight, show similar changes in body composition, and do not display any improvements in insulin sensitivity or whole body glucose tolerance. These studies were conducted using breeder chow diets and matched low- vs. high-fat diets. While glycogen accumulation in the liver is reduced in IKKε mice, lipid storage in liver is similar in IKKε mice and littermate controls. Our results using IKKε mice suggest that the primary action of this kinase to impact insulin sensitivity during weight gain lies predominantly within extrahepatic tissues.
超重和肥胖状态的发生和进展会引起内分泌和免疫变化。核因子-κB 激酶-ε（IKKε）抑制剂最初被描述为一种诱导型蛋白激酶；全身性基因缺失或该激酶的全身药物靶向治疗可改善小鼠的胰岛素敏感性和葡萄糖耐量。为了研究与体重增加相关的 IKKε 的主要作用部位，我们描述了第一个在肝脏中具有条件性缺失 IKKε 的小鼠品系（IKKε）。IKKε 小鼠及其同窝对照小鼠体重增加，体成分发生相似变化，胰岛素敏感性或全身葡萄糖耐量没有任何改善。这些研究使用繁殖饲料和匹配的低脂与高脂饮食进行。虽然 IKKε 小鼠肝脏中的糖原积累减少，但肝内脂质储存与 IKKε 小鼠和同窝对照小鼠相似。我们使用 IKKε 小鼠的结果表明，该激酶在体重增加期间影响胰岛素敏感性的主要作用部位主要位于肝外组织。
