Thompson Janet A, Krajnak Kristine, Johnston Richard A, Kashon Michael L, McKinney Walter, Fedan Jeffrey S
Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, United States.
Toxicol Rep. 2021 Dec 7;9:12-21. doi: 10.1016/j.toxrep.2021.12.001. eCollection 2022.
Adipose tissue (AT) plays a central role in the maintenance of whole-body energy homeostasis through release of adipokines. High-fat Western diet (HFWD)-consumption contributes to obesity, disruption of adipocyte metabolism, chronic systemic inflammation, and metabolic dysfunction (MetDys). MetDys is associated with impaired lung function, pulmonary hypertension, and asthma. Thirty-five percent of adults in the U.S. have MetDys, yet the impact of MetDys on susceptibility to occupational hazards is unknown. The aim of this study was to determine the potential of HFWD-consumption to alter inhaled crystalline silica dust-induced metabolic responses. Six-wk old male F344 rats were fed a HFWD (45 kcal % fat, sucrose 22.2 % by weight) or standard rat chow (STD, controls), and exposed to silica-inhalation (6 h/d, 5 d/wk, 39 d; Min-U-Sil 5®, 15 mg/m) or filtered air. Indices of MetDys and systemic inflammation were measured at 0, 4, and 8 wk following cessation of silica exposure. At 8 wk post-exposure, silica reduced serum leptin and adiponectin levels, and increased arterial pulse frequency. HFWD-consumption induced weight gain, altered adipokines, liver, kidney, and pancreatic function, and increased tail artery blood flow. At 8 wk in HFWD + SIL-treated animals, the levels of serum pro-inflammatory cytokines (IFN-γ, CXCL-1, TNF-α, IL-1β, IL-4, IL-5, IL-6, IL-10 and IL-13) were increased compared to STD + SIL but were less than HFWD + AIR-induced levels. In conclusion, consumption of a HFWD altered silica-induced metabolic responses and silica exposure disrupted AT endocrine function. These findings demonstrate previously unknown interactions between HFWD-consumption and occupational silica exposure.
脂肪组织（AT）通过释放脂肪因子在维持全身能量稳态中发挥核心作用。食用高脂肪的西方饮食（HFWD）会导致肥胖、脂肪细胞代谢紊乱、慢性全身炎症和代谢功能障碍（MetDys）。MetDys与肺功能受损、肺动脉高压和哮喘有关。美国35%的成年人患有MetDys，但MetDys对职业危害易感性的影响尚不清楚。本研究的目的是确定食用HFWD改变吸入结晶二氧化硅粉尘诱导的代谢反应的可能性。六周龄雄性F344大鼠喂食HFWD（45千卡%脂肪，蔗糖22.2%重量）或标准大鼠饲料（STD，对照），并暴露于二氧化硅吸入（6小时/天，5天/周，39天；Min-U-Sil 5®，15毫克/立方米）或过滤空气中。在停止二氧化硅暴露后的0、4和8周测量MetDys和全身炎症指标。暴露后8周，二氧化硅降低了血清瘦素和脂联素水平，并增加了动脉脉搏频率。食用HFWD导致体重增加，改变了脂肪因子、肝脏、肾脏和胰腺功能，并增加了尾动脉血流量。在HFWD + SIL处理的动物中，8周时血清促炎细胞因子（IFN-γ、CXCL-1、TNF-α、IL-1β、IL-4、IL-5、IL-6、IL-10和IL-13）水平与STD + SIL相比有所升高，但低于HFWD + AIR诱导的水平。总之，食用HFWD改变了二氧化硅诱导的代谢反应，二氧化硅暴露破坏了AT内分泌功能。这些发现证明了食用HFWD与职业性二氧化硅暴露之间以前未知的相互作用。
