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Secondhand Smoke Induces Liver Steatosis through Deregulation of Genes Involved in Hepatic Lipid Metabolism.


  • 影响因子:4.1830
  • DOI:10.3390/ijms21041296
  • 作者列表:"Tommasi S","Yoon JI","Besaratinia A
  • 发表时间:2020-02-14

:We investigated the role of secondhand smoke (SHS) exposure, independently of diet, in the development of chronic liver disease. Standard diet-fed mice were exposed to SHS (5 h/day, 5 days/week for 4 months). Genome-wide gene expression analysis, together with molecular pathways and gene network analyses, and histological examination for lipid accumulation, inflammation, fibrosis, and glycogen deposition were performed on the liver of SHS-exposed mice and controls, upon termination of exposure and after one-month recovery in clean air. Aberrantly expressed transcripts were found in the liver of SHS-exposed mice both pre- and post-recovery in clean air (n = 473 vs. 222). The persistent deregulated transcripts (n = 210) predominantly affected genes and functional networks involved in lipid metabolism as well as in the regulation of the endoplasmic reticulum where manufacturing of lipids occurs. Significant hepatic fat accumulation (steatosis) was observed in the SHS-exposed mice, which progressively increased as the animals underwent recovery in clean air. Moderate increases in lobular inflammation infiltrates and collagen deposition as well as loss of glycogen were also detectable in the liver of SHS-exposed mice. A more pronounced phenotype, manifested as a disrupted cord-like architecture with foci of necrosis, apoptosis, inflammation, and macrovesicular steatosis, was observed in the liver of SHS-exposed mice post-recovery. The progressive accumulation of hepatic fat and other adverse histological changes in the SHS-exposed mice are highly consistent with the perturbation of key lipid genes and associated pathways in the corresponding animals. Our data support a role for SHS in the genesis and progression of metabolic liver disease through deregulation of genes and molecular pathways and functional networks involved in lipid homeostasis.


: 我们研究了二手烟 (SHS) 暴露在慢性肝病发展中的作用,与饮食无关。标准饮食喂养的小鼠暴露于 SHS (5 h/天,5 天/周,持续 4 个月)。全基因组基因表达分析,连同分子通路和基因网络分析,以及脂质蓄积、炎症、纤维化、在 SHS 暴露小鼠和对照组的肝脏上进行糖原沉积,在暴露终止时和清洁空气中恢复一个月后。在清洁空气恢复前和恢复后 SHS 暴露小鼠的肝脏中发现异常表达的转录本 (n = 473 vs.222)。持续失调的转录本 (n = 210) 主要影响参与脂质代谢以及发生脂质制造的内质网调控的基因和功能网络。在暴露于 SHS 的小鼠中观察到显著的肝脏脂肪堆积 (脂肪变性),随着动物在清洁空气中恢复而逐渐增加。在 SHS 暴露小鼠的肝脏中也可检测到小叶炎症浸润和胶原沉积以及糖原丢失的中度增加。在 SHS 暴露小鼠恢复后的肝脏中观察到更明显的表型,表现为破坏的索样结构,病灶为坏死、凋亡、炎症和大泡状脂肪变性。SHS 暴露小鼠肝脏脂肪的进行性蓄积和其他不良组织学变化与相应动物关键脂质基因和相关通路的扰动高度一致。我们的数据支持 SHS 通过调控参与脂质稳态的基因和分子通路以及功能网络在代谢性肝病发生和进展中的作用。



作者列表:["Hone M","Nugent AP","Walton J","McNulty BA","Egan B"]

METHODS:BACKGROUND:Given the importance of habitual dietary protein intake, distribution patterns and dietary sources in the aetiology of age-related declines of muscle mass and function, the present study examined these factors as a function of sex and age in Irish adults aged 18-90 years comprising The National Adult Nutrition Survey (NANS). METHODS:In total, 1051 (males, n = 523; females, n = 528) undertook a 4-day semi-weighed food diary. Total, body mass relative intake and percentage contribution to total energy intake of dietary protein were determined in addition to protein distribution scores (PDS), as well as the contribution of food groups, animal- and plant-based foods to total protein intake. RESULTS:Total and relative protein intake [mean (SD)] were highest in those aged 18-35 years [96 (3) g day , 1.32 (0.40) g kg day ], with lower protein intakes with increasing age (i.e. in adults aged ≥65 years [82 (22) g, 1.15 (0.34) g kg day , P < 0.001 for both]. Differences in protein intake between age groups were more pronounced in males compared to females. Protein distribution followed a skewed pattern for all age groups [breakfast, 15 (10) g; lunch, 30 (15) g; dinner, 44 (17) g]. Animal-based foods were the dominant protein source within the diet [63% (11%) versus 37% (11%) plant protein, P < 0.001]. CONCLUSIONS:Protein intake and the number of meals reaching the purported threshold for maximising post-prandial anabolism were highest in young adults, and lower with increasing age. For main meals, breakfast provided the lowest quantity of protein across all age categories and may represent an opportunity for improving protein distribution, whereas, in older adults, increasing the number of meals reaching the anabolic threshold regardless of distribution pattern may be more appropriate.

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作者列表:["Bonomi AG","Ten Hoor GA","De Morree HM","Plasqui G","Sartor F"]

METHODS:BACKGROUND:Low cardiorespiratory fitness (CRF) increases risk of all-cause mortality and cardiovascular events. Periodic CRF assessment can have an important preventive function. OBJECTIVE:To develop a protocol-free method to estimate CRF in daily life based on heart rate (HR) and body acceleration measurements. METHODS:Acceleration and HR data were collected from 37 subjects (M=49%) while performing a standardized laboratory activity protocol (sitting, walking, running, cycling) and during a 5-days free-living monitoring period. CRF was determined by oxygen uptake (VO2max) during maximal exercise testing. A doubly-labeled water validated equation was used to predict total energy expenditure (TEE) from acceleration data. A fitness index was defined as the ratio between TEE and HR (TEE-pulse). Activity recognition techniques were used to process acceleration features and classify sedentary, ambulatory and other activity types. Regression equations based on TEE-pulse data from each activity type were developed to predict VO2max. RESULTS:TEE-pulse measured within each activity type of the laboratory protocol was highly correlated to VO2max (r from 0.74 to 0.91). Averaging the outcome of each activity-type specific equation based on TEE-pulse from the laboratory data led to accurate estimates of VO2max (RMSE: 300.0 mlO2/min or 10%). The difference between laboratory and free-living determined TEE-pulse was 3.7 ± 11% (r =0.85). The prediction method preserved the prediction accuracy when applied to free-living data (RMSE: 367 mlO2/min or 12%). CONCLUSIONS:Measurements of body acceleration and HR can be used to predict VO2max in daily life. Activity-specific prediction equations are needed to achieve highly accurate estimates of CRF.

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作者列表:["Farr S","Stankovic B","Hoffman S","Masoudpoor H","Baker C","Taher J","Dean A","Anakk S","Adeli K"]

METHODS:OBJECTIVE:Postprandial dyslipidemia is a common feature of insulin resistant states and contributes to increased cardiovascular disease risk. Recently, bile acids have been recognized beyond their emulsification properties as important signaling molecules that promote energy expenditure, improve insulin sensitivity, and lower fasting lipemia. While bile acid receptors have become novel pharmaceutical targets, their effects on postprandial lipid metabolism remain unclear. Here we investigated the potential role of bile acids in regulation of postprandial chylomicron production and triglyceride excursion. Approach and Results: Healthy C57BL/6 mice were given an intraduodenal infusion of taurocholic acid (TA) under fat-loaded conditions and circulating lipids were measured. Targeting of bile acid receptors was achieved with GW4064, a synthetic agonist to the farnesoid X receptor (FXR), and with deoxycholic acid (DCA), an activator of the Takeda G-protein-coupled receptor 5. TA, GW4064, and DCA treatments all lowered postprandial lipemia. FXR agonism also reduced intestinal triglyceride content and activity of microsomal triglyceride transfer protein, involved in chylomicron assembly. Importantly, TA effects (but not DCA) were largely lost in FXR knockout mice. These bile acid effects are reminiscent of the anti-diabetic hormone glucagon-like peptide-1 (GLP-1). While the GLP-1 receptor agonist exendin-4 retained its ability to acutely lower postprandial lipemia during bile acid sequestration and FXR deficiency, it did raise hepatic expression of the rate limiting enzyme for bile acid synthesis. CONCLUSIONS:Bile acid signaling may be an important mechanism of controlling dietary lipid absorption and bile acid receptors may constitute novel targets for the treatment of postprandial dyslipidemia.

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