Endocrine Abstracts

Thyroid hormones (THs) are known to regulate both lipid, glucose, and cholesterol metabolism. These effects have led to biochemical and molecular studies on the roles that they and their metabolites have on these processes. Additionally, TH analogs have been developed to improve metabolic conditions such as hypertriglyceridemia hypercholesterolemia, and obesity while minimizing side effects such as tachycardia and osteoporosis that occur in hyperthyroidism. Typically, these analogs have preferential binding to the TH receptor beta isoform or preferential uptake by the liver. It now has been appreciated that THs also may have beneficial effects for the treatment of non-alcoholic fatty liver disease (NAFLD). We and others observed that TH and TH analogs decreased hepatosteatosis in animal and cell culture models of NAFLD by stimulating autophagy and b-oxidation of fatty acids. Additionally, we found that intrahepatic triiodothyronine (T3) levels were decreased and serum T3 levels were normal in an animal model of NAFLD. These findings suggested that there may be ‘liver-specific hypothyroidism’ in NAFLD so serum TH levels alone may not be sufficient to determine the TH status within the liver in this condition. We also have shown that the TH metabolite, diiodothyronine (T2), decreased hepatosteatosis in rats fed high fat diet by stimulating autophagy and acylcarnitine flux. We recently completed a pilot clinical study showing that low dose levothyroxine supplementation was able to decrease hepatosteatosis in euthyroid adult Asian men with diabetes. Taken together, these findings suggest that TH supplementation or the employment of TH metabolites and analogs may have therapeutic promise for the treatment of NAFLD and other metabolic conditions.