3,5-DIIODO-L-THYRONINE (T2) ADMINISTRATION AFFECTS VISCERAL ADIPOSE TISSUE INFLAMMATORY STATE IN RAT RECEIVING LONG-LASTING HIGH-FAT DIET

Objectives: 3,5 diiodo-L-thyronine (T2), a naturally existing iodothyronine, has biological effects, but the underlying mechanisms are poorly understood. Its actions exerted in counteracting fat accumulation in rats on a high fat diet (HFD) are particularly relevant. Visceral white adipose tissue accumulation is associated with the inflammatory response that plays an important role in the development of many diseases related to obesity. In the present study, we focused our attention on T2 actions aimed at improving the adverse effects of long-lasting HFD such as the adipocyte inflammatory response. Methods: For this purpose, three groups of rats were used: i) receiving a standard diet for 14 weeks; ii) receiving a HFD for 14 weeks, and iii) receiving a HFD for 14 weeks with a simultaneous daily injection of T2 for the last 4 weeks. In the adipose tissue, the expression of pro and anti-inflammatory cytokines, hypoxia and angiogenesis markers, and oxidative damage of DNA were measured. Results: The results showed that T2 administration ameliorated the expression profiles of pro- and anti-inflammatory cytokines, reduced macrophage infiltration in white adipose tissue and influenced their polarization. Moreover, T2 improved the expression of hypoxia markers, all altered in HFD rats, and reduced angiogenesis by decreasing the pro-angiogenic miR126 expression. Additionally, T2 reduced the oxidative damage of DNA, known to be associated to the inflammatory status. Conclusions: This study demonstrates that T2 is able to counteract some adverse effects caused by a long-lasting HFD and to produce beneficial effects on inflammation.