3,5 Diiodo-l-Thyronine (T2) Promotes the Browning of White Adipose Tissue in High-Fat Diet-Induced Overweight Male Rats Housed at Thermoneutrality

Abstract

The conversion of white adipose cells into beige adipose cells is known as browning, a process affecting energy metabolism. It has been shown that 3,5 diiodo-l-thyronine (T2), an endogenous metabolite of thyroid hormones, stimulates energy expenditure and a reduction in fat mass. In light of the above, the purpose of this study was to test whether in an animal model of fat accumulation, T2 has the potential to activate a browning process and to explore the underlying mechanism. Three groups of rats were used: (i) receiving a standard diet for 14 weeks; (ii) receiving a high-fat diet (HFD) for 14 weeks; and (iii) receiving a high fat diet for 10 weeks and being subsequently treated for four weeks with an HFD together with the administration of T2. We showed that T2 was able to induce a browning in the white adipose tissue of T2-treated rats. We also showed that some miRNA (miR133a and miR196a) and MAP kinase 6 were involved in this process. These results indicate that, among others, the browning may be another cellular/molecular mechanism by which T2 exerts its beneficial effects of contrast to overweight and of reduction of fat mass in rats subjected to HFD.

3,5-T2—A Janus-Faced Thyroid Hormone Metabolite Exerts Both Canonical T3-Mimetic Endocrine and Intracrine Hepatic Action

“…Subsequently, the Naples teams, with investigator Goglia, added more endpoints to demonstrate rapid 3,5-T2 action, such as increased glucose consumption in muscle, which might involve sirtuin signaling (91). Several pathways involved in mediation of 3,5-T2 effects were subsequently studied using gene expression, functional, and proteomic readouts, especially for rat liver and muscle (92,93) while comparable control data on potentially adverse effects of 3,5-T2 concentrations resulting in changes of liver and muscle metabolism were not systematically presented.…”

Analysis of Tks4 Knockout Mice Suggests a Role for Tks4 in Adipose Tissue Homeostasis in the Context of Beigeing

“…Therefore, the molecular and genetic mechanisms governing obesity are intensively studied, with the goal of improving the management and treatment of obesity-associated diseases [2,3,4]. Such studies have identified numerous biochemical factors that control fat storage [5,6,7] and differences in fat depot physiologies [8], with the ultimate goal of developing novel strategies to regulate adipose tissue homeostasis.…”

Toll-Like Receptors-2 and -4 in Graves’ Disease—Key Players or Bystanders?

“…Kawakami et al demonstrated that TLR-2 and TLR-4 receptors in the salivary gland of the disease patients show a significantly higher level of expression than in the control group [27]. Studies of recent years indicate that abnormal activation of the innate immune response, and consequently a number of changes resulting from this fact, may have a significant impact on the pathogenesis of autoimmune thyroid diseases (AITD) [28,29,30,31,32,33,34,35,36,37,38,39,40]. In light of the above data, TLRs play an important role in the development of autoimmune diseases such as SLE, type 1 diabetes or RA [17,18,19,20,21,22,23,24,25,26,27,28].…”