JANUS – The God that named January

Happy New Year 2018 dear readers!

We are back and we would like to inaugurate this year’s post series with the presentation of the FOIE GRAS network’s promotional video, that is available in the Project’s Youtube channel. This video was recorded during the 1st Network Summer School, the topic of our very first blog post, and has also been shared in EU-funded R&I projects playlist of the EU Science & Innovation Channel.

This was the first time getting in front of a camera for most of us, and it was a very exciting and interesting experience that will certainly come in handy in the years to come. The FOIE GRAS network was designed to put emphasis on the development of transferrable skills that prepare early-stage researchers, like us, not just for the methodologies and techniques used in science, but in skills that will allow us to reach the general public and get our biomedical research through to other areas of knowledge and levels of expertise, namely the industry, public health policy, funding agencies or the media.

The filming part, but not the fun of video production, ended with the summer school. The footage was edited in the following months and after some versions and final touches, we published it in December. One of the most interesting parts of this journey was the development of the animations for the video. Rui Tavares, a very talented illustrator working with the FOIE GRAS project, created the animation that can be seen in the video as well as the other visual aids featured in this short production.

Panels_Video.jpg

In trying to find the best way to communicate or represent in a few seconds the different progression stages of NAFLD (Non-Alcoholic Fatty Liver Disease), we explored several concepts. In the end, the version that we thought was most understandable and informative is the one appearing in the video. A slight variation that was a close competitor is the image below:

NAFLD_v5.jpg

Can you spot the difference?

Yep, indeed, this one has a double-faced individual in the middle section of the scheme. So let’s go over the different parts to explain what this Janus thing is doing here. At the very left we have the representation of a healthy human liver and right underneath a zoom-in of the cells within this liver. The next liver is what is known as a fatty liver and it constitutes the first stage of NAFLD. The fatty liver is bigger than the rest, a phenomenon that is known as hepatomegalia, and also has a yellowish aspect. The cells of the fatty liver have large droplets of fat inside them, which is what gives this yellow color to the liver. The second stage of NAFLD is NASH (Non-Alcoholic Steatohepatitis), in which there is an inflammatory reaction that is activated in part by the excess of fat inside the liver cells. Some of these cells die and the liver, in an attempt to regenerate its own tissue, produces fibrosis, a protein matrix (blue fibers in the image) that aims at repair. If fibrosis continues, it eventually disorganizes the cell structure of the liver and impairs its functions. At this stage, cirrhosis, the only solution is to undergo a liver transplant.

Besides the level of the livers, with the different color, size and textures, and the cellular level, with the different histological presentations of the progression stages, the scheme also includes arrows of different size, color and direction. These are meant to represent the frequency and reversibility of the steps; 1 in every 4 individuals in the world has fatty liver, and therefore has been through the first yellow arrow. Of the fatty liver patients, approximately 30% go on to develop NASH, which is still reversible if the person undergoes treatment (i.e. healthy nutrition and active lifestyle). Lastly, about 20% of the people that suffers from NASH eventually develop cirrhosis, a point of no return in which the damage on the architecture of the liver cannot be reversed (red arrow).

And last but not least, actually the most important part of the scheme is the lower section. The biomedical research performed at FOIE GRAS focuses on the energetic remodeling in NAFLD, and therefore in trying to identify how the excess of fat and the inflammation affect the mitochondria, the cellular components that convert food molecules into energy for body function. At the beginning, the liver cells detect an increase of fat inside them, so they signal to the mitochondria to speed-up and get rid of the fats (mitochondrial function line going up). Besides working harder, the cells also create more mitochondria by making them split in two in an attempt to become more efficient. Unfortunately, there is a point in which this state is unsustainable and the mitochondria start to produce toxic substances and can no longer keep up with the pace.

Janus was a Roman god with two faces and is a symbol of transitions and passages, of beginnings and endings. The month of January, named after Janus, symbolizes the start of the year and gives a sense of new dawn to this particular way we have of measuring time. In biology, Janus is used to refer to molecules or processes that can have both positive and negative effects both coming from the consequences of the same action. In our case, the seemingly beneficial increase in mitochondrial function (by increasing the activity and number of mitochondria) is the process responsible for the energetic dysfunction in later stages of the disease; the increased activity creates large amount of toxic substances that lead to mitochondrial dysfunction and cell death.

The exact mechanisms by which this Janus effect takes place, or the best targets to treat these molecular processes are some of the biomedical underpinnings of NAFLD that FOIE GRAS is trying to unravel.

May Janus bless us with a fruitful and productive 2018 and long life to mitochondria!

THE AUTHOR

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Mireia Alemany i Pagès (ESR-13) is currently working at the Center for Neuroscience and Cell Biology (CNC) at the University of Coimbra, Portugal. Her project focuses on raising awareness on NAFLD through Science Communication.

 

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