Ambient particulate air pollution induces oxidative stress and alterations of mitochondria and gene expression in brown and white adipose tissues

Abstract

BackgroundPrior studies have demonstrated a link between air pollution and metabolic diseases such as type II diabetes. Changes in adipose tissue and its mitochondrial content/function are closely associated with the development of insulin resistance and attendant metabolic complications. We investigated changes in adipose tissue structure and function in brown and white adipose depots in response to chronic ambient air pollutant exposure in a rodent model.MethodsMale ApoE knockout (ApoE-/-) mice inhaled concentrated fine ambient PM (PM < 2.5 μm in aerodynamic diameter; PM2.5) or filtered air (FA) for 6 hours/day, 5 days/week, for 2 months. We examined superoxide production by dihydroethidium staining; inflammatory responses by immunohistochemistry; and changes in white and brown adipocyte-specific gene profiles by real-time PCR and mitochondria by transmission electron microscopy in response to PM2.5 exposure in different adipose depots of ApoE-/- mice to understand responses to chronic inhalational stimuli.ResultsExposure to PM2.5 induced an increase in the production of reactive oxygen species (ROS) in brown adipose depots. Additionally, exposure to PM2.5 decreased expression of uncoupling protein 1 in brown adipose tissue as measured by immunohistochemistry and Western blot. Mitochondrial number was significantly reduced in white (WAT) and brown adipose tissues (BAT), while mitochondrial size was also reduced in BAT. In BAT, PM2.5 exposure down-regulated brown adipocyte-specific genes, while white adipocyte-specific genes were differentially up-regulated.ConclusionsPM2.5 exposure triggers oxidative stress in BAT, and results in key alterations in mitochondrial gene expression and mitochondrial alterations that are pronounced in BAT. We postulate that exposure to PM2.5 may induce imbalance between white and brown adipose tissue functionality and thereby predispose to metabolic dysfunction.

Ambient Fine Particulate Matter Induces Apoptosis of Endothelial Progenitor Cells Through Reactive Oxygen Species Formation

“…ROS could function as signaling molecules in PM-trigged autophagy in human epithelia A549 cells [36]. Oxidative stress could be triggered by PM and result in alterations in mitochondrial gene expression in brown adipose tissue [37]. Clinical studies indicated that ROS-initiated oxidative stress and inflammation by PM was closely related to the pediatric asthma [38].…”

Exercise regulation of adipose tissue

“…2). Some studies have demonstrated increased BAT activity with exercise, [61][62][63][64][65][66] others showed no change in BAT activity, [67][68][69][70] while a third set of studies reported a decrease in BAT activity with exercise. 32,[71][72][73][74] Exercise increases BAT activity Studies in rats have demonstrated that 6-8 wks of swim training for 2-3 hours per day resulted in increased blood flow to BAT and increased responsiveness to norepinephrine stimulation.…”

Diabetes and Metabolic Syndrome

“…Multiple abnormalities in mitochondrial rich BAT have been noted in C57BL/6 mice in response to long durations (10 months) of PM 2.5 exposure and in ApoE −/− mice over shorter durations (2 months) (Xu et al 2011a , b ). Visible decreases in BAT mass and decreased mitochondrial size in BAT depots were observed in long term PM 2.5 exposure compared to FA (Xu et al 2011b ). These changes were accompanied by increased oxidative and nitrosative stress in BAT, along with Phase II antioxidant gene induction including NF-E2-related factor 2 (Nrf2), NAD(P)H quinone oxidoreductase 1 and glutamate-cysteine ligase modifi er subunit.…”