Abstract
Objective Thyroid hormones have been associated with a hepatic lipid lowering effect and thyroid
function has been shown to play a substantial role in development of non-alcoholic
fatty liver disease. Hepatic lipid droplets differ in the number, size and molecular
properties depending on metabolic state or pathological condition. However, in how
far thyroid hormone deficiency affects hepatic lipid droplet morphology and molecular
properties is still poorly understood. Therefore, we performed a study in mice using
a lithogenic diet model of steatohepatitis and modulated the thyroid hormone status.
Methods Male and female three months old C57BL/6 mice were divided into a euthyroid (control),
a lithogenic (litho) and a lithogenic+thyroid hormone deficient (litho+hypo) group
and treated for six weeks. Hepatic transmission electron microscopy and gene expression
analysis of lipid-droplet associated proteins were performed.
Results Increased mean diameters of hepatic lipid droplets and a shift towards raised electron-density
in lipid droplets was observed under thyroid hormone deficiency. Furthermore thyroid
hormone deficiency altered hepatic expression of genes involved in lipophagy and triacylglycerol
mobilization. Interestingly, while the impact of thyroid hormone deficiency on lipid
droplet morphology seems to be sex-independent, hepatic lipid droplet-associated gene
expression differed significantly between both sexes.
Conclusion This study demonstrates that thyroid hormone deficiency alters hepatic lipid droplet
morphology and hepatic gene expression of lipid droplet-associated proteins in a lithogenic
diet mouse model of steatohepatitis.
Key words
thyroid dysfunction - lipid droplets - hepatocytes - hepatic lipid accumulation -
metabolic liver diseases
