Two papers which closely link.
The first, from 2018, identifies a novel thyroid hormone transporter.
The second builds on that to try to identify why fatty liver issues occur. But no real answers yet.
We have had many members say that they suffer from fatty liver disease. This might be worth a read.
Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation
Nature Communications volume 9, Article number: 4455 (2018)
Abstract
Thyroid dysfunction is an important public health problem, which affects 10% of the general population and increases the risk of cardiovascular morbidity and mortality. Many aspects of thyroid hormone regulation have only partly been elucidated, including its transport, metabolism, and genetic determinants. Here we report a large meta-analysis of genome-wide association studies for thyroid function and dysfunction, testing 8 million genetic variants in up to 72,167 individuals. One-hundred-and-nine independent genetic variants are associated with these traits. A genetic risk score, calculated to assess their combined effects on clinical end points, shows significant associations with increased risk of both overt (Graves’ disease) and subclinical thyroid disease, as well as clinical complications. By functional follow-up on selected signals, we identify a novel thyroid hormone transporter (SLC17A4) and a metabolizing enzyme (AADAT). Together, these results provide new knowledge about thyroid hormone physiology and disease, opening new possibilities for therapeutic targets.
Open access:
nature.com/articles/s41467-...
Induction of steatosis in primary human hepatocytes recapitulates key pathophysiological aspects of metabolic dysfunction-associated steatotic liver disease
Highlights
•Increasing prevalence of MASLD warrants new cellular models for drug development
•In vitro model of steatotic primary human hepatocytes recapitulates MASLD phenotypes
•Firsocostat rescued steatosis and insulin resistance, providing proof of concept
Background & Aims
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of chronic liver disease. Its limited treatment options warrant novel pre-clinical models for target selection and drug validation. We have established and extensively characterized a primary human steatotic hepatocyte in vitro model system that could guide treatment strategies for MASLD.
Methods
Cryopreserved primary human hepatocytes from five donors varying in sex and ethnicity were cultured with free fatty acids (FFA) in 3D collagen sandwich for 7 days and the development of MASLD was followed by assessing classical hepatocellular functions. As proof of concept, the effects of the drug Firsocostat (GS-0976) on in vitro MASLD phenotypes were evaluated.
Results
Incubation with FFA induced steatosis, insulin resistance, mitochondrial dysfunction, inflammation, and alterations in prominent human gene signatures similar to patients with MASLD, indicating the recapitulation of human MASLD in this system. As the application of Firsocostat rescued clinically observed fatty liver disease pathologies, it highlights the ability of the in vitro system to test drug efficacy and potentially characterize their mode of action.
Conclusions
Altogether, our human MASLD in vitro model system could guide the development and validation of novel targets and drugs for the treatment of MASLD.
Impact and implications
Due to low drug efficacy and high toxicity, a clinical treatment option for MASLD is limited. To facilitate earlier stop-go decisions in drug development, we have established a primary human steatotic hepatocyte in vitro model. As the model recapitulates clinically relevant MASLD characteristics at high phenotypic resolution, it can serve as a pre-screening platform and guide target identification and validation in MASLD therapy.
Open access:
Need help I have thyroid hormone absorption issues! 
Potential Hormonal issues
