Aim: 

High-fat diet induced insulin resistance (IR) is accompanied by ectopic lipid/ triglycerides deposition in peripheral tissues. 3,5-diiodo-L-thyronine (T2) when administered simultaneously with a high-fat diet (HFD) prevents body weight gain and liver steatosis without inducing thyrotoxicity in rats. we studied the effects of T2 on systemic HFD-induced IR and the ability of T2 in preventing fat accumulation in skeletal muscle improving insulin signalling.

Results: 

Glucose and insulin tolerance tests in HFD rats showed lower kinetics of glucose clearance when compared with control standard diet fed rats (N). T2 administration prevented development of IR being the glucose and insulin tolerance tests normal in HFD+T2 rats. Skeletal muscle triglyceride content significantly increased in the HFD rats compared to N (3.4 ± 0.46 and 1.76 ± 0.22 mg/ml, respectively) and was significantly reduced by T2-treatment, being the value (2.41 ± 0.55 mg/m) not significantly different from N. Insulin-induced AKT phosphorylation, was significantly decreased in HFD rats vs N, whereas it was increased in T2-treated ones. An upregulation of adipocyte differentiation-related protein (ADRP) was observed following T2-treatment in accordance with an unaltered insulin signalling pathway in skeletal muscle.

Conclusion: 

The results indicated that, by reducing triglycerides accumulation and preserving insulin sensitivity, T2 has the therapeutic potential for preventing IR-related metabolic disorders.