期刊
NATURE MEDICINE
卷 17, 期 9, 页码 1121-U130出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.2421
关键词
-
资金
- US National Institutes of Health (NIH) [DK084065, DK080000, OD006850]
- American Diabetes Association [7-08-MN-25]
- NIH [DK089098, DK072033, DK090320, DK052989, AR47901, P30 AR42687]
Previous studies have proposed roles for hypothalamic reactive oxygen species (ROS) in the modulation of circuit activity of the melanocortin system(1,2). Here we show that suppression of ROS diminishes pro-opiomelanocortin (POMC) cell activation and promotes the activity of neuropeptide Y (NPY)- and agouti-related peptide (AgRP)-co-producing (NPY/AgRP) neurons and feeding, whereas ROS-activates POMC neurons and reduces feeding. The levels of ROS in POMC neurons were positively correlated with those of leptin in lean and ob/ob mice, a relationship that was diminished in diet-induced obese (DIO) mice. High-fat feeding resulted in proliferation of peroxisomes and elevated peroxisome proliferator-activated receptor gamma (PPAR-gamma) mRNA levels within the hypothalamus. The proliferation of peroxisomes in POMC neurons induced by the PPAR-gamma agonist rosiglitazone decreased ROS levels and increased food intake in lean mice on high-fat diet. Conversely, the suppression of peroxisome proliferation by the PPAR antagonist GW9662 increased ROS concentrations and c-fos expression in POMC neurons. Also, it reversed high-fat feeding-triggered elevated NPY/AgRP and low POMC neuronal firing, and resulted in decreased feeding of DIO mice. Finally, central administration of ROS alone increased c-fos and phosphorylated signal transducer and activator of transcription 3 (pStat3) expression in POMC neurons and reduced feeding of DIO mice. These observations unmask a previously unknown hypothalamic cellular process associated with peroxisomes and ROS in the central regulation of energy metabolism in states of leptin resistance.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据