3,5-Diiodo-l-thyronine modulates the expression of genes of lipid metabolism in a rat model of fatty liver

Abstract

Recent reports demonstrated that 3,5-diiodo-L-thyronine (T 2 ) was able to prevent lipid accumulation in the liver of rats fed a high-fat diet (HFD). In this study, we investigated how the rat liver responds to HFD and T 2 treatment by assessing the transcription profiles of some genes involved in the pathways of lipid metabolism: oxidation, storage and secretion. The mRNA levels of the peroxisome proliferator-activated receptors (PPARa, PPARg and PPARd), and of their target enzymes acyl-CoA oxidase and stearoyl-CoA desaturase were evaluated by real-time RT-PCR. Moreover, the expression of the adipose triglyceride lipase involved in lipid mobilisation, of the main PAT proteins acting in lipid droplet (LD) turnover, and of apoprotein B (apo B), the major protein component of very low-density lipoproteins (VLDLs) were analysed. Overall, our data demonstrated that T 2 administration to HFD rats counteracts most of the hepatic transcriptional changes that occurred in response to the excess exogenous fat. In particular, our results suggest that T 2 may prevent the pathways leading to lipid storage in LDs, promote the processes of lipid mobilisation from LDs and secretion as VLDL, in addition to the stimulation of pathways of lipid oxidation. In conclusion, our findings might give an insight into the mechanisms underlying the anti-steatotic ability of T 2 and help to define the potential therapeutic role of T 2 for preventing or treating liver steatosis.

3,5-T2 alters murine genes relevant for xenobiotic, steroid, and thyroid hormone metabolism

“…3,5-T 2 might stimulate hepatic cholesterol synthesis accompanied by increased secretion of biliary cholesterol, the main route for cholesterol elimination from the body. This would be in line with published data showing the antisteatotic ability of 3,5-T 2 application in HFD rats (Mollica et al 2009, Grasselli et al 2012.…”

“…Most of the beneficial effects of 3,5-T 2 reported on mitochondrial function, lipid mobilization, and fatty acid oxidation were observed in experimental models of obesity or chronic hypothyroidism in rodents, mainly rats , Grasselli et al 2012, Cavallo et al 2013, Silvestri et al 2010, while only scarce data exist regarding the effects of 3,5-T 2 on metabolism in euthyroid mammals on standard or on HFD in a mouse model (Goldberg et al 2012). …”

3,5-Diiodo-L-Thyronine Modifies the Lipid Droplet Composition in a Model of Hepatosteatosis

“…T 2 has been demonstrated able to reduce fat overload in the hepatocyte [16,19,20,21,41], and this lipid-lowering action is not mediated by thyroid hormone receptors [21]. In the present study, we demonstrate that the lipid-lowering action of T 2 is associated with modifications in the fatty acid composition of LDs in particular through a stimulation of the oxidative metabolism of saturated fatty acids (SFAs).…”

Stress-Related Weight Gain: Mechanisms Involving Feeding Behavior, Metabolism, Gut Microbiota and Inflammation

“…The lipolytic effects of thyroid hormones in adipose and non-adipose tissues are also widely known. More recently, the thyroid hormone derivative 3,5-diiodothyronine (T2) has been shown to activate lipidlowering mechanisms in target tissues [44,45]. Therefore, the inhibition of thyroid function by GCs may represent another mechanism linking chronic stress, dysmetabolism and obesity.…”