ABSTRACT: Thyroid hormones (THs) influence adipose tissue development and metabolism. They regulate both adipocyte proliferation and differentiation and, as they increase the metabolic rate, may be helpful for obesity treatment. However, due to their cardiotoxic effects, like tachycardia and arrhythmia, their use is limited to hypothyroid obese patients. Interestingly, some TH metabolites have been recently shown to possess the same beneficial metabolic effects as THs without any negative effect. The biogenic amine 3-Iodothyronamine (T1AM), for example, affects carbohydrate and lipid metabolism without undesirable side effects. In mice T1AM exhibits cardiac effects opposite to those associated with thyroid hormones, like bradycardia, and, in isolated working rat hearts, produces a rapid, reversible, dose-dependent decrease in cardiac output, aortic pressure and coronary flow. Intraperitoneal injections of T1AM, moreover, induce reduction of RQ from 0.9 to 0.7, both in mice and Djungarian hamsters, indicating that carbohydrate utilisation is reduced and energy requirements are covered by lipid consumption. Ketone bodies in the urine and the significant loss of body fat mass confirm that lipids are predominantly used to cover the energy requirements in response to T1AM administration. The molecular mechanisms by which T1AM favors the lipid rather than glucose catabolism are not known, but it is possible to envisage changes in gene expression, given the delayed and long-lasting phenotypic effects. The complete RQ shift, for example, is reached 4.5 h after the T1AM injection and persists at least for 24 h. In this paper we analyzed the gene expression profiles in subcutaneous adipose tissue and in liver of eight rats chronically treated with T1AM as compared with eight untreated rats. Many genes linked to lipid metabolism, adipogenesis and angiogenesis appeared modulated by T1AM, thus contributing to explain the T1AM phenotypic effects observed in rodents. Furthermore, T1AM influenced the expression of several genes relating to lipoprotein metabolism that provide new insights on T1AM mechanism of action, like, for example, the regulation of cholesterol homeostasis.
