Lipid lowering effects of iodothyronines: In vivo and in vitro studies on rat liver

Abstract

Non-alcoholic fatty liver disease (NAFLD) is emerging as one of the most common liver diseases, leading to the increasing interest for new therapeutic approaches for its treatment. NAFLD primarily depends on a hypercaloric and/or unbalanced diet leading to overweight and obesity. The liver, in fact, plays a central role in lipid metabolism by importing free fatty acids from the blood and synthesizing, storing, oxidizing and exporting lipids. Furthermore, the liver is the target for the thyroid hormones, thyroxine (T₄) and 3,3’,5-triiodo-L-thyronine (T₃), that stimulate the basal metabolic rate and lead to body weight loss. In the last decade, other iodothyronines have been shown to possess biological relevance and play some thyromimetic activities; in particular, 3,5-diiodo-L-thyronine (T₂) gained large interest. The global effect of iodothyronines on liver lipid metabolism results from the balance between direct and indirect actions on the hepatocyte, leading to stimulation of lipid synthesis, oxidation and autophagy. In this review, the results so far obtained on both in vivo and in vitro models of hepatosteatosis are summarized in order to obtain an updated picture of the lipid-lowering effects of iodothyronines on mammalian liver.

Keywords: Iodothyronines, Liver steatosis, Lipid metabolism, Non-alcoholic fatty liver disease, Hepatocytes

Core tip: This review summarizes the recent insights about the mechanisms underlying the lipid lowering action of iodothyronines. In the last decades, extensive studies investigated the possible use of iodothyronines in the treatment of obesity and dysmetabolic syndromes. Since the pharmacological use of thyroid hormones has found severe limitations because of their thyrotoxic effects, the identification of iodothyronines retaining anti-obesity and hypolipemic efficacies, while being devoid of thyrotoxicity, gained great interest. The review discusses the recent studies employing both in vivo and in vitro models of hepatosteatosis, with particular attention to the in vitro studies demonstrating the direct anti-steatotic effect of iodothyronines.