Dumaine Jennifer E, Ashley Noah T
School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Biology, Western Kentucky University, Bowling Green, KY, USA.
PeerJ. 2018 Feb 19;6:e4423. doi: 10.7717/peerj.4423. eCollection 2018.
Obesity and sleep fragmentation (SF) are often co-occurring pro-inflammatory conditions in patients with obstructive sleep apnea. Leptin is a peptide hormone produced by adipocytes that has anorexigenic effects upon appetite while regulating immunity. The role of leptin in mediating inflammatory responses to SF is incompletely understood. Male C57BL/6j (lean) and ob/ob mice (leptin-deficient mice exhibiting obese phenotype) were subjected to SF or control conditions for 24 h using an automated SF chamber. Trunk blood and tissue samples from the periphery (liver, spleen, fat, and heart) and brain (hypothalamus, prefrontal cortex, and hippocampus) were collected. Quantitative PCR was used to determine relative cytokine gene expression of pro-inflammatory (IL-1β, TNF-α) and anti-inflammatory (TGF-β1) cytokines. Enzyme-linked immunosorbent assay (ELISA) was used to determine serum corticosterone concentration. Ob/ob mice exhibited elevated cytokine gene expression in liver (TNF-α, TGF-β1), heart (TGF-β1), fat (TNF-α), and brain (hippocampus, hypothalamus, prefrontal cortex: IL-1β, TNF-α) compared with wild-type mice. Conversely, leptin deficiency decreased pro-inflammatory cytokine gene expression in heart (IL-1β, TNF-α). SF significantly increased IL-1β and TNF-α gene expression in fat and TGF-β1 expression in spleen relative to controls, but only in wild-type mice. SF increased basal serum corticosterone regardless of genotype. Taken together, these findings suggest that leptin deficiency affects cytokine gene expression differently in the brain compared to peripheral tissues with minimal interaction from acute SF.
肥胖与睡眠片段化（SF）在阻塞性睡眠呼吸暂停患者中常常是同时出现的促炎状态。瘦素是一种由脂肪细胞产生的肽类激素，对食欲有抑制作用，同时调节免疫。瘦素在介导对睡眠片段化的炎症反应中的作用尚未完全明确。使用自动睡眠片段化舱，将雄性C57BL/6j（瘦型）和ob/ob小鼠（表现出肥胖表型的瘦素缺乏小鼠）置于睡眠片段化或对照条件下24小时。采集躯干血液以及外周组织（肝脏、脾脏、脂肪和心脏）和大脑（下丘脑、前额叶皮质和海马体）的组织样本。采用定量PCR测定促炎细胞因子（IL-1β、TNF-α）和抗炎细胞因子（TGF-β1）的相对细胞因子基因表达。采用酶联免疫吸附测定（ELISA）法测定血清皮质酮浓度。与野生型小鼠相比，ob/ob小鼠在肝脏（TNF-α、TGF-β1）、心脏（TGF-β1）、脂肪（TNF-α）和大脑（海马体、下丘脑、前额叶皮质：IL-1β、TNF-α）中的细胞因子基因表达升高。相反，瘦素缺乏降低了心脏中促炎细胞因子基因的表达（IL-1β、TNF-α）。与对照组相比，睡眠片段化显著增加了脂肪中IL-1β和TNF-α的基因表达以及脾脏中TGF-β1的表达，但仅在野生型小鼠中出现。无论基因型如何，睡眠片段化均增加了基础血清皮质酮水平。综上所述，这些发现表明，与外周组织相比，瘦素缺乏对大脑中细胞因子基因表达的影响不同，且急性睡眠片段化的相互作用最小。
