In this study, we aimed to determine the relative effectiveness of common dietary polyphenols or the isoquinoline alkaloid berberine in protecting against molecular mechanisms underlying non-alcoholic fatty liver disease (NAFLD) involving changes to cellular lipid metabolism and bioenergetics. In a model of steatosis using HepG2 hepatocytes, exposure of the cells to 1.5 mM oleic acid (OA) for 24 h caused steatosis and distorted cell morphology, induced the expression of mRNA for enzymes that are involved in lipogenesis and fatty acid oxidation (FAS and CPT1A), and impaired indices of aerobic energy metabolism (PPARγ mRNA expression, mitochondrial membrane potential (MMP), and galactose-supported ATP production). Co-treatment with 10 µM of selected polyphenols all strongly protected against the steatosis and changes in cell morphology. All polyphenols, except cyanidin, inhibited the effects on FAS and PPARγ and further increased CPT1A1 expression, suggesting a shift toward increased β-oxidation. Resveratrol, quercetin, catechin, and cyanidin, however not kuromanin or berberine, ameliorated the decreases in MMP and galactose-derived ATP. Berberine was unique in worsening the decrease in galactose-derived ATP. In further investigations of the mechanisms involved, resveratrol, catechin, and berberine increased SIRT1 enzyme activity and p-AMPKα^Thr172 protein, which are involved in mitochondrial biogenesis. In conclusion, selected polyphenols all protected against steatosis with similar effectiveness, however through different mechanisms that increased aerobic lipid metabolism and mitochondrial function.

Measurements of nitryl chloride (ClNO₂) and its precursors (O₃, NO₂, particulate chloride) were made in 2014–2016 at three contrasting locations in the United Kingdom: Leicester, Penlee Point and Weybourne. ClNO₂ was observed at all sites and in every season, with the highest concentrations between 00:00 and 04:00 GMT. The median nocturnal concentration of ClNO₂ ranged between the detection limit (4.2 ppt) and 139 ppt. A clear seasonal cycle, with maxima in spring and winter, and significant differences between locations in the same season were observed. The main source of particulate chloride was sea salt aerosol (including at Leicester, ∼200 km from the coast). In general, ClNO₂ levels were controlled by the concentrations of O₃ and NO₂, rather than by the uptake and reaction of N₂O₅ with particulate chloride. Under these conditions, the seasonality and geographical distribution of ClNO₂ can be explained in terms of O₃‐limited and NO₂‐limited regimes affecting the formation of the N₂O₅ precursor. A global version of the GEOS‐Chem model at medium resolution (2° × 2.5°) was not able to fully capture the observed seasonality of ClNO₂, mostly because the model overestimated the concentrations of the precursors, particularly of nocturnal O₃. A higher‐resolution (0.25° × 0.3125°) version of GEOS‐Chem showed better agreement with the observations, although it still overestimated ClNO₂ concentrations during summer.

Halogens (Cl, Br) have a profound influence on stratospheric ozone (O₃). They (Cl, Br and I) have recently also been shown to impact the troposphere, notably by reducing the mixing ratios of O₃and OH. Their potential for impacting regional air-quality is less well understood. We explore the impact of halogens on regional pollutants (focussing on O₃) with the European grid of the GEOS-Chem model (0.25° × 0.3125°). It has recently been updated to include a representation of halogen chemistry. We focus on the summer of 2015 during the ICOZA campaign at the Weybourne Atmospheric Observatory on the North Sea coast of the UK. Comparisons between these observations together with those from the UK air-quality network show that the model has some skill in representing the mixing ratios/concentration of pollutants during this period. Although the model has some success in simulating the Weybourne ClNO₂observations, it significantly underestimates ClNO₂observations reported at inland locations. It also underestimates mixing ratios of IO, OIO, I₂and BrO, but this may reflect the coastal nature of these observations. Model simulations, with and without halogens, highlight the processes by which halogens can impact O₃. Throughout the domain O₃mixing ratios are reduced by halogens. In northern Europe this is due to a change in the background O₃advected into the region, whereas in southern Europe this is due to local chemistry driven by Mediterranean emissions. The proportion of hourly O₃above 50 nmol mol⁻¹in Europe is reduced from 46% to 18% by halogens. ClNO₂from N₂O₅uptake onto sea-salt leads to increases in O₃mixing ratio, but these are smaller than the decreases caused by the bromine and iodine. 12% of ethane and 16% of acetone within the boundary layer is oxidised by Cl. Aerosol response to halogens is complex with small (∼10%) reductions in PM_2.5in most locations. A lack of observational constraints coupled to large uncertainties in emissions and chemical processing of halogens make these conclusions tentative at best. However, the results here point to the potential for halogen chemistry to influence air quality policy in Europe and other parts of the world.

Background: Substantially elevated blood D-lactate (DLA) concentrations are associated with neurocardiac toxicity in humans and animals. The neurological symptoms are similar to inherited or acquired abnormalities of pyruvate metabolism. We hypothesized that DLA interferes with mitochondrial utilization of L-lactate and pyruvate in brain and heart. Methods: Respiration rates in rat brain, heart and liver mitochondria were measured using DLA, LLA and pyruvate independently and in combination. Results: In brain mitochondria, state 3 respiration was 53% and 75% lower with DLA as substrate when compared with LLA and pyruvate, respectively (p < 0.05). Similarly in heart mitochondria, state 3 respiration was 39% and 86% lower with DLA as substrate when compared with LLA or pyruvate, respectively (p < 0.05). However, state 3 respiration rates were similar between DLA, LLA and pyruvate in liver mitochondria. Combined incubation of DLA with LLA or pyruvate markedly impaired state 3 respiration rates in brain and heart mitochondria (p < 0.05) but not in liver mitochondria. DLA dehydrogenase activities were 61% and 51% lower in brain and heart mitochondria compared to liver, respectively, whereas LLA dehydrogenase activities were similar across all three tissues. An LDH inhibitor blocked state 3 respiration with LLA as substrate in all three tissues. A monocarboxylate transporter inhibitor blocked respiration with all three substrates. Conclusions: DLA was a poor respiratory substrate in brain and heart mitochondria and inhibited LLA and pyruvate usage in these tissues. Further studies are warranted to evaluate whether these findings support, in part, the possible neurological and cardiac toxicity caused by high DLA levels.