Regulation of genes involved in the metabolic adaptation of murine microglial cells in response to elevated HIF-1α mediated activation.

Microglia cells are activated in response to different stress signals. Several metabolic adaptations underlie microglia activation in the brain. Among these, in conditions like ischemic stroke and, hypoxic stress stimuli activate microglia cells. Hypoxic stress is mediated by HIF-1α. Although HIF-1α has been implicated in the alteration of metabolic pathways, changes in microglia lipid metabolism during M1 activation of microglia induced by elevated HIF-1α levels are yet to be understood. This can also merit interest in the development of novel targets to mitigate chronic inflammation. Our study aims to elucidate the transcriptional regulation of metabolic pathways in microglia cells during HIF-1α mediated activation. To study the adaptations in the metabolic pathways we induced microglia activation, by activating HIF-1α. Here, we show that microglia cells activated in response to elevated HIF-1α require ongoing lipogenesis and fatty acid breakdown. Notably, autophagy is activated during the initial stages of microglia activation. Inhibition of autophagy in activated microglia affects their viability and phagocytic activity. Collectively, our study expands the understanding of the molecular link between autophagy, lipid metabolism, and inflammation during HIF-1α mediated microglial activation that can lead to the development of promising strategies for controlling maladaptive activation states of microglia responsible for neuroinflammation. Together, our findings suggest that the role of HIF-1α in regulating metabolic pathways during hypoxia in microglia is beyond optimization of glucose utilization and distinctly regulates lipid metabolism during pro-inflammatory activation.

Current Understanding on the Role of Lipids in Macrophages and Associated Diseases.

Lipid metabolism is the major intracellular mechanism driving a variety of cellular functions such as energy storage, hormone regulation and cell division. Lipids, being a primary component of the cell membrane, play a pivotal role in the survival of macrophages. Lipids are crucial for a variety of macrophage functions including phagocytosis, energy balance and ageing. However, functions of lipids in macrophages vary based on the site the macrophages are residing at. Lipid-loaded macrophages have recently been emerging as a hallmark for several diseases. This review discusses the significance of lipids in adipose tissue macrophages, tumor-associated macrophages, microglia and peritoneal macrophages. Accumulation of macrophages with impaired lipid metabolism is often characteristically observed in several metabolic disorders. Stress signals differentially regulate lipid metabolism. While conditions such as hypoxia result in accumulation of lipids in macrophages, stress signals such as nutrient deprivation initiate lipolysis and clearance of lipids. Understanding the biology of lipid accumulation in macrophages requires the development of potentially active modulators of lipid metabolism.

Polystyrene nanoplastics dysregulate lipid metabolism in murine macrophages in vitro.

Micro and nanoplastics are one of the major emerging environmental contaminants. Their impact on human health is less explored. There are several in vitro studies on their cellular uptake and accumulation, where micro and nanoplastics were mostly reported to be non-cytotoxic. The effects caused by the direct contact of nanoplastics with the immune system, especially at the cellular level is less known. Here we report that RAW 264.7 macrophages undergo differentiation into lipid laden foam cells when exposed to polystyrene nanoplastics (50 µg/mL). We found that exposure of RAW 264.7 macrophages to sulfate-modified polystyrene nanoplastics results in the accumulation of lipid droplets in the cytoplasm leading to foam cell formation. Exposure to high concentration of polystyrene nanoplastics (100 and 200 µg/mL) results in increased reactive oxygen species and impair lysosomes in macrophages. The exposure of BV2 microglial cells to polystyrene nanoplastics (50 µg/mL) induces lipid accumulation. In addition, our results indicate the role of polystyrene nanoplastics in altering the lipid metabolism in murine macrophages in vitro. In the present study we reported that polystyrene nanoplastics stabilized with anionic surfactants can be potent stimuli for lipotoxicity and foam cell formation leading to the pathogenesis of atherosclerosis posing major threat for animal and human health.

Differential sensitivity of marine algae Dunaliella salina and Chlorella sp. to P25 TiO2 NPs.

The use of P25 TiO2 NPs in consumer products, their release, and environmental accumulation will have harmful effects on the coastal ecosystems. The sensitivity to TiO2 NPs may vary depending on the structural property and physiological mechanism of algal species. Therefore, the present study investigates the differences in sensitivity of two marine algae, Dunaliella salina and Chlorella sp., towards P25 TiO2 NPs. Among the two species, Chlorella sp. was more sensitive to TiO2 NPs than Dunaliella salina. The different working concentrations of TiO2 NPs, 0.1, 1, and 10 mg L-1, were selected based on the EC50 value. The EC50 value of TiO2 NPs for Dunaliella salina was found to be 1.8 and 13.3 mg L-1 under UV-A and dark conditions, respectively. The EC50 value of TiO2 NPs for Chlorella sp. was found to be 1.6 and 5.0 mg L-1 under UV-A and dark conditions, respectively. The decrease in cell viability was significantly higher for Chlorella sp. compared to Dunaliella salina at all concentrations except 0.1 mg L-1. The cellular viability data was in correlation with the oxidative stress markers such as total ROS and LPO. A concentration-dependent increase in ROS and lipid peroxidation was noted under UV-A exposure, which was higher in Chlorella sp. compared to Dunaliella salina. The decrease in the SOD activity with NP concentration was more in Dunaliella salina than Chlorella sp. under both conditions, whereas Chlorella sp. showed increased CAT activity with increasing concentration. The uptake of TiO2 NPs was more in Chlorella sp. than Dunaliella salina.