3-Iodothyronamine Affects Thermogenic Substrates’ Mobilization in Brown Adipocytes

Abstract

We investigated the effect of 3-iodothyronamine (T1AM) on thermogenic substrates in brown adipocytes (BAs). BAs isolated from the stromal fraction of rat brown adipose tissue were exposed to an adipogenic medium containing insulin in the absence (M) or in the presence of 20 nM T1AM (M+T1AM) for 6 days. At the end of the treatment, the expression of p-PKA/PKA, p-AKT/AKT, p-AMPK/AMPK, p-CREB/CREB, p-P38/P38, type 1 and 3 beta adrenergic receptors (β1–β3AR), GLUT4, type 2 deiodinase (DIO2), and uncoupling protein 1 (UCP-1) were evaluated. The effects of cell conditioning with T1AM on fatty acid mobilization (basal and adrenergic-mediated), glucose uptake (basal and insulin-mediated), and ATP cell content were also analyzed in both cell populations. When compared to cells not exposed, M+T1AM cells showed increased p-PKA/PKA, p-AKT/AKT, p-CREB/CREB, p-P38/P38, and p-AMPK/AMPK, downregulation of DIO2 and β1AR, and upregulation of glycosylated β3AR, GLUT4, and adiponectin. At basal conditions, glycerol release was higher for M+T1AM cells than M cells, without any significant differences in basal glucose uptake. Notably, in M+T1AM cells, adrenergic agonists failed to activate PKA and lipolysis and to increase ATP level, but the glucose uptake in response to insulin exposure was more pronounced than in M cells. In conclusion, our results suggest that BAs conditioning with T1AM promote a catabolic condition promising to fight obesity and insulin resistance.

Substantial impact of 3-iodothyronamine (T1AM) on the regulations of fluorescent thermoprobe-measured cellular temperature and natriuretic peptide expression in cardiomyocytes

“…The mechanisms underlying the intracellular temperature regulation of cardiomyocytes remain largely unknown. UCPs, particularly UCP1 (which is predominantly expressed in brown adipocytes) have roles in thermogenesis, although a previous study reported that T1AM did not significantly affect the UCP1 expression in brown adipose tissue 25 . Meanwhile, two isoforms (UCP2 and UCP3, but not UCP1) are located in the heart.…”

Redox Properties of 3-Iodothyronamine (T1AM) and 3-Iodothyroacetic Acid (TA1)

“…We previously demonstrated that UCP-1 protein levels were similar in M + T1AM and M cells [ 17 ]. Instead, in this study, as reported in Figure 3 (panels a and b), the M + TA1 cells showed significantly lower UCP-1 protein expression ( Figure 3 , panel a, b; ** p < 0.01) than the M cells.…”

“…The interscapular brown adipose tissue was isolated from one-month-old male Wistar rats (Envigo, San Pietro al Natisone, Italy) according to [ 17 ]. For this study, we received permission from the Ethical Committee for Animal Health (176/2017-PR) from the Italian Ministry of Health, and the experimental procedures were carried on in compliance with the European Convention for the Protection of Vertebrate Animals used for Experimental and Other Scientific Purposes (ETS No.…”

“…Consistently with this latter, the activation of SIRT1 is a fingerprint signaling of known antioxidants [ 15 , 16 ]. Lastly, in our recent work, [ 17 ] we reported that brown adipocytes (BAs) differentiated in the presence of 20 nM T1AM resulted in a cell population (M + T1AM cells) showing a pro-oxidant metabolism compared to cells not exposed to T1AM (M cells).…”

3-iodothyronamine inhibits apoptosis induced by myocardial ischemia reperfusion via the Akt/FoxO1 signaling pathway

“…Original Article 3-iodothyronamine inhibits apoptosis induced by myocardial ischemia reperfusion via the Akt/FoxO1 signaling pathway 3-iodothyronamine (T1AM) is an endogenous thyroid hormone derivative with opposing biological effects to those of thyroid hormones (6). Administration of T1AM can lead to a rapid reduction in body temperature, body metabolism (7,8), and heart rate (9). Furthermore, it has therapeutic potential for the treatment of metabolic (10), cardiovascular (11,12), and neurological diseases (13,14).…”