The world of toxicology is changing.  Researchers have been exploring new ways to test how harmful substances affect living things.  One exciting development is the use of three-dimensional (3D) cell cultures.  These 3D models are better at mimicking real tissues than the old flat (2D) cell layers.  However, using 3D fish cell models in toxicology studies is still rare.  This is where zebrafish liver spheroids come in.  They are tiny, 3D balls of cells that can help scientists understand how toxins affect fish.  These spheroids are made from zebrafish liver cells and are about 400 micrometers in diameter after seven days of growth.  They show some interesting differences compared to the old 2D cell layers.

    First, let's talk about lipids.  Lipids are fats and fatty substances.  In these spheroids, there are more neutral lipids like cholesterol esters and diacylglycerols.  This means the cells are storing more fat.  At the same time, the genes responsible for making fats are less active.  This suggests that the cells are shifting from making fats to storing them.  This is a big deal because it shows that the spheroids are more like real liver tissue.  Real liver tissue stores fat, and these spheroids are doing the same.

    The spheroids also have a different mix of membrane lipids.  Membrane lipids are the fats that make up the cell's outer layer.  In the spheroids, there are more phosphatidylcholines compared to phosphatidylethanolamines.  This is important because it shows that the cells are organizing themselves in a way that's more like real tissue.  Plus, there are more phospholipids with long-chain polyunsaturated fatty acids, like docosahexaenoic acid (DHA).  DHA is an omega-3 fatty acid that's crucial for brain health.  So, these spheroids are not just storing fat; they're storing the good kind of fat.

    Now, let's talk about how these spheroids react to toxins.  When exposed to a substance called β-naphthoflavone (BNF), the spheroids showed a much higher increase in the expression of a gene called cyp1a.  This gene is involved in breaking down toxins.  The spheroids had a 650-fold increase, while the 2D cell layers only had a 57-fold increase.  This shows that the spheroids are better at handling toxins, making them a more realistic model for testing how harmful substances affect living things.

    So, what does all this mean?  It means that zebrafish liver spheroids are a big step forward in toxicology testing.  They're more like real liver tissue, and they react to toxins in a more realistic way.  This makes them a valuable tool for scientists studying how harmful substances affect fish and, by extension, other animals and even humans.  The study also highlights the importance of looking at lipids when studying 3D cell models.  Lipids play a big role in how cells work, and understanding them can give scientists a better picture of what's happening in these models.

    However, it's not all perfect.  While these spheroids show promise, they're still not exactly like real liver tissue.  They're a model, and like all models, they have their limits.  But they're a step in the right direction.  As scientists continue to study and improve these models, they'll become even more useful tools for understanding the effects of toxins on living things.

ZEBRAFISH LIVER SPHEROIDS

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