Jeon Yoonjeong, Aja Susan, Ronnett Gabriele V, Kim Eun-Kyoung
Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science & Technology, Daegu, Republic of Korea.
Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Biochem Biophys Res Commun. 2016 Feb 19;470(4):818-23. doi: 10.1016/j.bbrc.2016.01.115. Epub 2016 Jan 21.
The regulation of food intake is important for body energy homeostasis. Hypothalamic insulin signaling decreases food intake by upregulating the expression of anorexigenic neuropeptides and downregulating the expression of orexigenic neuropeptides. INS-2, a Mn(2+) chelate of 4-O-(2-amino-2-deoxy-β-D-galactopyranosyl)-3-O-methyl-D-chiro-inositol, acts as an insulin mimetic and sensitizer. We found that intracerebroventricular injection of INS-2 decreased body weight and food intake in mice. In hypothalamic neuronal cell lines, INS-2 downregulated the expression of neuropeptide Y (NPY), an orexigenic neuropeptide, but upregulated the expression of proopiomelanocortin (POMC), an anorexigenic neuropeptide, via modulation of the AKT-forkhead box-containing protein-O1 (FoxO1) pathway. Pretreatment of these cells with INS-2 enhanced the action of insulin on downstream signaling, leading to a further decrease in NPY expression and increase in POMC expression. These data indicate that INS-2 reduces food intake by regulating the expression of the hypothalamic neuropeptide genes through the AKT-FoxO1 pathway downstream of insulin.
食物摄入的调节对于机体能量稳态至关重要。下丘脑胰岛素信号通过上调厌食性神经肽的表达和下调促食欲神经肽的表达来减少食物摄入。INS-2是4-O-(2-氨基-2-脱氧-β-D-吡喃半乳糖基)-3-O-甲基-D-手性肌醇的锰(2+)螯合物，具有胰岛素模拟物和增敏剂的作用。我们发现，脑室内注射INS-2可降低小鼠体重和食物摄入量。在下丘脑神经元细胞系中，INS-2通过调节AKT-含叉头框蛋白O1（FoxO1）途径，下调促食欲神经肽神经肽Y（NPY）的表达，但上调厌食性神经肽阿黑皮素原（POMC）的表达。用INS-2预处理这些细胞可增强胰岛素对下游信号的作用，导致NPY表达进一步降低，POMC表达增加。这些数据表明，INS-2通过胰岛素下游的AKT-FoxO1途径调节下丘脑神经肽基因的表达来减少食物摄入。
