Docosahexaenoic fatty acid reduces the pro‐inflammatory response induced by IL-1β in astrocytes through inhibition of NF-κB and AP-1 transcription factor activation

Background Astrocytes are responsible for a broad range of functions that maintain homeostasis in the brain. However, their response to the pro-inflammatory cytokines released by activated microglia in various neurological pathologies may exacerbate neurodegenerative processes. Accumulating evidence suggests that omega-3 docosahexaenoic fatty acid (DHA) has an anti-inflammatory effect in various cell cultures studies and in a variety of neurological disorders. In this study we examined the mechanism involved in the inhibition of the pro-inflammatory response by DHA in astrocytes treated with IL-1β. Methods and results Activation of the transcription factors NF-κB and AP-1 was measured in IL-1β-treated primary astrocytes incubated with various concentrations of DHA. COX-2 and iNOS protein expression was determined by Western blot, and TNF-α and IL-6 secretion was measured using ELISA-based assays. DHA treatment inhibited translocation of p65NF-κB to the nucleus, significantly lowered p65NF-κB protein level and fluorescence of p65NF-κB in the nucleus, reduced dose-dependently IκB protein phosphorylation, and the binding of the AP-1 transcription factor members (c-Jun/c-Fos) to the specific TPA-response element (TRE) of DNA. In addition, the expression of pro-inflammatory COX-2 and iNOS proteins was downregulated and TNF-α and IL-6 secretion was also reduced. Conclusions These results indicate that DHA is a powerful factor that reduces the pro-inflammatory response in astrocytes. Consequently, successful introduction of DHA into the astrocyte membranes can attenuate neuroinflammation, which is a key factor of age-related neurodegenerative disorders.

ADDITION OF Aurantiochytrium sp. MEAL IN THE DIET AFFECTS IMMUNITY AND THERMAL SHOCK RESISTANCE OF THE PACIFIC WHITE SHRIMP

This paper reports the evaluation of digestibility, immunological parameters, and resistance to thermal shock at low temperature in Litopenaeus vannamei fed diets with diferent Aurantiochytrium sp. meal additions (0; 0.5; 1 and 2%). First, the apparent digestibility coefficient of the ingredient was determined. The digestibility of the microalgae meal was high for protein (74.90%); around 60% for lipids, and for docosahexaenoic fatty acid (DHA) it was 55.61%. After, shrimp rearing with the feed additive was carried out in a clear water system, containing 25 shrimp (initial weight: 4.89 ± 0.27 g) per 400 L tank. Feeding occurred four times a day. After a three-week period, immunological parameters were evaluated and thermal shock was performed. Animals fed 0.5% and 2% of the microalgae Aurantiochytrium sp. showed higher survival to thermal shock. In immunological analyses, the serum agglutiniting titer was higher (p <0.05) in the 0.5 and 2% additions of the microalgae meal, and the phenoloxidase activity (PO) was higher in the 1% addition (p <0.05). It is concluded that there is good utilization of the nutrients of Aurantiochytrium sp. meal by L. vannamei and its addition to the diet (0.5 and 1%) increased shrimp resistance to thermal shock.

Docosahexaenoic fatty acid-containing phospholipids affect plasma membrane susceptibility to disruption by bacterial toxin-induced macroapertures

Metabolic studies and animal knockout models point to the critical role of polyunsaturated docosahexaenoic acid (22:6, DHA)-containing phospholipids (PLs) in physiology. Here, we study the impact of DHA-PLs on the dynamics of transendothelial cell macroapertures (TEMs) tunnels triggered by the RhoA GTPase inhibitory exotoxin C3 from Clostridium botulinum. Through lipidomic analyses, we show that primary human umbilical vein endothelial cells (HUVECs) subjected to DHA-diet undergo a 6-fold DHA-PLs enrichment in plasma membrane at the expense of monounsaturated OA-PLs. In contrast, OA-diet had almost no effect on PLs composition. Consequently, DHA treatment increases the nucleation rate of TEMs by 2-fold that we ascribe to a reduction of cell thickness. We reveal that the global transcellular area of cells remains conserved through a reduction of the width and lifetime of TEMs. Altogether, we reveal a homeostasis between plasma membrane DHA-PLs content and large-scale membrane dynamics.