Docosahexaenoic acid significantly stimulates immediate early response genes and neurite outgrowth.

Docosahexaenoic acid (22:6n - 3, DHA) is known to enhance neurogenesis. However, the immediate-early effect of DHA on neurogenesis is not fully elucidated. We studied the effect of DHA supplementation (10 and 30 microM) on morphological and molecular changes at different time points of nerve growth factor (NGF, 50 ng/ml)-induced differentiation of PC12 (pheochromocytoma) cells. Cells were analyzed throughout the differentiation process (2 h, 1, 2, 3, 4, and 10 days), for neurite outgrowth (light microscopy and computer image analysis), and for mRNA levels of the immediate molecular differentiation markers Egr1, Egr3, PC3 and PC4 (quantitative real-time PCR). DHA induced significant accelerated neurite outgrowth beginning as early as 2 h post-DHA supplementation and throughout differentiation. Transcripts of the neurogenesis immediate early biomarkers Egr3 and PC3 were significantly (P < 0.05) elevated following DHA supplementation within 0.5 and 1 h post-supplementation (respectively). In conclusion, we show that DHA significantly stimulates immediate-early neurogenesis events, as is evident by both morphological and molecular markers.

Palmitate induced lipoapoptosis of exocrine pancreas AR42J cells.

Chronic surplus of dietary consumption, typical to obesity, results in overflow of fat to non-adipose tissues. Intracellular accumulation of fat in non-adipose tissues is associated with cellular dysfunction and cell death and ultimately contributes to the pathogenesis of chronic diseases. The influence of fat overflow on the exocrine pancreas is not known. The purpose of this research was to study the lipotoxic and lipoapoptotic effect of prolonged (72 h) long chain saturated palmitic fatty acid (0.1 mM) on the survival of exocrine pancreas AR42J cells. We demonstrate that chronic exposure of AR42J cells to palmitic acid results in significant increase in triglycerides accumulation (up to 25% of cells area), compared to untreated cultures. Lipid accumulation prompted a typical apoptotic process, demonstrated by both DNA fragmentation and condensed chromatin appearance (DAPI staining). Quantitative real-time PCR studies demonstrated that prolonged palmitic acid supplementation induced down-regulation of the anti-apoptotic Bcl2 mRNA levels (22%) and up-regulation of the pro-apoptotic Bax mRNA levels (300%), leading to disruption of the pro/anti apoptotic balance (Bax/Bcl2=3). No major change was detected in iNOS mRNA expression. In conclusion, prolonged exposure to saturated palmitic acid induces lipoapoptosis in exocrine pancreatic AR42J cells, through disturbance of the Bax/Bcl-2 balance.