Effects of 3,5-diiodo-L-thyronine on the liver of high fat diet fed rats

Abstract

Experimental studies have highlighted that the administration of 3,5-diiodo-L-thyronine (T2) to rats fed diets rich in lipids induces a decrease of cholesterol and triglycerides plasma levels and body weight (BW) without inducing liver steatosis. On the basis of these observations we carried out some experimental in vivo studies to assess the effects of multiple high doses of T2 on the pituitary thyroid axis of rats fed diet rich in lipids. Fifteen male Wistar rats were divided into three groups of five animals each. The first group (N group) received standard diet, the second group was fed with a high fat diet (HFD group), while the third group (HFDT2 group) was additionally given T2 intraperitoneally at a dose level of 70 mg/100 g of BW three times a week up to four weeks. At the end of the treatment, blood sample from each animal was collected, centrifuged and the serum was stored at -20°C. The serum concentrations of thyroidstimulating hormone (TSH), triiodothyronine, thyroxine, adrenocorticotropic hormone, triglycerides, cholesterol, glucose, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase were then determined. In addition, liver of rats was examined by histology in order to assess the presence and degree of steatosis. The administration of T2 to rats fed with a high fat diet suppressed TSH secretion (P=0.013) while no steatosis was observed in the liver of these animals. Our data show that multiple administrations of high doses of T2 to rats fed diets rich in lipid inhibit TSH secretion and prevent the onset of liver steatosis in these animals.

Genomic and Non-Genomic Mechanisms of Action of Thyroid Hormones and Their Catabolite 3,5-Diiodo-L-Thyronine in Mammals

“…As discussed below, indeed, 3,5-T2 has some T3-like effects [182][183][184][185][186][187] in the absence of thyrotoxic side effects, at least when used at low concentrations [20,188]. On the contrary, at higher concentrations, it has been reported to suppress TSH and the HPT axis [189][190][191] and even to cause adverse cardiac effects similar to those observed in hyperthyroidism [190].…”

“…As discussed above, the treatment with 3,5-T2 may prevent the damage caused by HFD and reduce the circulating levels of LDL and TAG, as well as hepatic steatosis in overweight patients. It has been reported that the hormone may also reduce a pre-existing accumulation of fat in the rat liver [191]. In humans, a few studies have confirmed that the administration of 3,5-T2 can increase the resting metabolic rate, also reducing adiposity and body weight without side effects [250].…”

“…As summarized below, many experimental observations have shown that 3,5-T2 administration to rodents caused an increase in the resting metabolic rate (RMR) [185,197] and prevented overweight and insulin resistance induced by a high-fat diet (HFD) [198,199]. Furthermore, the administration of 3,5-T2 to HFD rats seems to protect animals from the onset of non-alcoholic fatty liver disease (NAFLD) [191], although this finding has been challenged by results obtained in Sprague-Dawley rats fed an unsaturated fat diet, in which 3,5-T2 failed to improve NAFLD and insulin sensitivity [200]. It is worth noting, however, that 3,5-T2 has been suggested to influence glucose metabolism not through effects on insulin sensitivity, but by reducing hepatic glucose transporters 2 (GLUT2) and glucose output from the liver [201].…”

“…A further problem arises from the degree of purity of commercial preparations of 3,5-T2, used as standards in the measurements; these preparations are, indeed, frequently contaminated with T3 [20,204]. Even with these limitations, 3,5-T2 is now widely considered a bioactive molecule with dose-dependent effects on physiological regulatory functions [20,59,113,191,[204][205][206][207][208][209][210][211].…”

“…Even with these limitations, 3,5-T2 is widely considered a bioactive molecule [20,59,113,191,[204][205][206][207][208][209][210][211]. Thus, in summary, the field is very promising and might offer important advancements in the therapy of obesity and related pathologies.…”