Fatty Li ver Disease has genetic and nutritional components.
The NHS says,
“Non-alcoholic fatty liver disease (NAFLD) is the term for a range of conditions caused by a build-up of fat in the liver. It's usually seen in people who are overweight or obese.”
“A healthy liver should contain little or no fat. It's estimated up to 1 in every 3 people in the UK has early stages of NAFLD, where there are small amounts of fat in their liver.”
“There's currently no specific medication for NAFLD, but making healthy lifestyle choices can help.”
Advances in the study of NAFLD have used a chimeric mouse, one that contains both normal cells and genetically manipulated.
An April 2021 study (on mice) by Baylor College of Medicine and Duke University of NAFLD said,
"NAFLD has been difficult to study mainly because we had no good animal model,"
"Our goal was to have a mouse model that would allow us to study the disorder and test potential treatments,"
"Applying our lab's years long expertise developing chimeric mouse models, those that combine both human and murine cells, we developed mice with livers that were part human and part murine."
"We were surprised by the striking differences we observed under the microscope,”
"In the same liver, the human liver cells were filled with fat, a typical characteristic of the human disease, while the mouse liver cells remained normal."
"For instance, when mice that received human liver cells fed on a high-fat diet, they started to show features of cholesterol metabolism that looked more like what a patient shows than what other previous animal models showed,"
"We made the same observation regarding genes that are regulated after the high-fat diet. All the analyses pointed at cholesterol metabolism being changed in this model in a way that closely replicates what we see in humans."
"We discovered that, compared to the normal mouse liver cells in our model, the fat-laden human liver cells had higher levels of gene transcripts for enzymes involved in cholesterol synthesis,"
"We wanted to see whether this was also the case in human NAFLD livers."
"Using the NAFLD consensome (1) we discovered that, indeed, compared to normal livers, NAFLD livers have consistently higher levels of cholesterol synthesis enzyme transcripts,”
"This is additional confirmation of the clinical accuracy of our NAFLD model."
"Here we have a model in which human liver cells respond like in humans. We propose that this model can be used to better understand NAFLD and to identify effective therapies."
Notes
consensome:
The Signaling Pathways Project, an integrated 'omics knowledgebase for mammalian cellular signaling pathways.
Scientific Data, 31 Oct 2019, 6(1):252
DOI: 10.1038/s41597-019-0193-4 PMID: 31672983 PMCID: PMC6823428
“the Signaling Pathways Project (SPP), which incorporates community classifications of signaling pathway nodes (receptors, enzymes, transcription factors and co-nodes) and their cognate bioactive small molecules.
We then mapped over 10,000 public transcriptomic or cistromic experiments to their pathway node or biosample of study.
To enable prediction of pathway node-gene target transcriptional regulatory relationships through SPP, we generated consensus 'omics signatures, or consensomes, which ranked genes based on measures of their significant differential expression or promoter occupancy across transcriptomic or cistromic experiments mapped to a specific node family.
Consensomes were validated using alignment with canonical literature knowledge, gene target-level integration of transcriptomic and cistromic data points, and in bench experiments confirming previously uncharacterized node-gene target regulatory relationships.”