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Open AccessArticle

Lipolytic Effects of 3-Iodothyronamine (T1AM) and a Novel Thyronamine-Like Analog SG-2 through the AMPK Pathway

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University of Alabama Birmingham School of Medicine, Cardiology Division, 901 19th St. S., Birmingham, AL 35209, USA
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Department of Pathology, University of Pisa, 56126 Pisa, Italy
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Department of Pharmacy, University of Pisa, 56126 Pisa, Italy
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Department of Nutritional Sciences, Texas Tech University, P.O. Box 41270, Lubbock, TX 79409, USA
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Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI, 53706-1544, USA
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Department of Integrative Biology, University of Wisconsin-Madison, 250 N. Mills St, Madison, WI 53706, USA
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(16), 4054; https://doi.org/10.3390/ijms20164054
Received: 27 July 2019 / Revised: 16 August 2019 / Accepted: 19 August 2019 / Published: 20 August 2019
(This article belongs to the Section Biochemistry)
3-Iodothyronamine (T1AM) and its synthetic analog SG-2 are rapidly emerging as promising drivers of cellular metabolic reprogramming. Our recent research indicates that in obese mice a sub-chronic low dose T1AM treatment increased lipolysis, associated with significant weight loss independent of food consumption. The specific cellular mechanism of T1AM’s lipolytic effect and its site of action remains unknown. First, to study the mechanism used by T1AM to gain entry into cells, we synthesized a fluoro-labeled version of T1AM (FL-T1AM) by conjugating it to rhodamine (TRITC) and analyzed its cellular uptake and localization in 3T3-L1 mouse adipocytes. Cell imaging using confocal microscopy revealed a rapid intercellular uptake of FL-T1AM into mitochondria without localization to the lipid droplet or nucleus of mature adipocytes. Treatment of 3T3-L1 adipocytes with T1AM and SG-2 resulted in decreased lipid accumulation, the latter showing a significantly higher potency than T1AM (10 µM vs. 20 µM, respectively). We further examined the effects of T1AM and SG-2 on liver HepG2 cells. A significant decrease in lipid accumulation was observed in HepG2 cells treated with T1AM or SG-2, due to increased lipolytic activity. This was confirmed by accumulation of glycerol in the culture media and through activation of the AMPK/ACC signaling pathways. View Full-Text
Keywords: 3-iodothyronamine (T1AM), thyroid hormone analogs; lipid metabolism; AMPK pathway; rhodamine (TRITC), cell imaging; metabolic reprogramming; mitochondria 3-iodothyronamine (T1AM), thyroid hormone analogs; lipid metabolism; AMPK pathway; rhodamine (TRITC), cell imaging; metabolic reprogramming; mitochondria
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Rogowski, M.; Bellusci, L.; Sabatini, M.; Rapposelli, S.; Rahman, S.M.; Chiellini, G.; Assadi-Porter, F.M. Lipolytic Effects of 3-Iodothyronamine (T1AM) and a Novel Thyronamine-Like Analog SG-2 through the AMPK Pathway. Int. J. Mol. Sci. 2019, 20, 4054.

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