3-Iodothyronamine Affects Thermogenic Substrates' Mobilization in Brown Adipocytes.

Manuela Gencarelli,Laura Raimondi,Costanza Mazzantini,Elisa Landucci,Daniela Buonvicino,Grazia Chiellini,Annunziatina Laurino

doi:10.3390/biology9050095

Manuela Gencarelli, Laura Raimondi + Show 5 more

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https://doi.org/10.3390/biology9050095

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Journal: Biology	Publication Date: May 4, 2020
Citations: 5	License type: CC BY 4.0

Affiliation: University of Florence, University of Pisa

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.

Highlights

We investigated the effect of 3-iodothyronamine (T1AM) on thermogenic substrates in brown adipocytes (BAs)
T1AM activates neuroprotective signaling including the activation of the AKT and protein kinase A (PKA) signaling [2,3]; it stimulates neuronal plasticity [4,5] and induces central-mediated reduction of body temperature without activating the brown adipose tissue [6,7,8]
M and M+T1AM cells (105 /well) on Day 6 were kept in DMEM with 0.1% bovine serum albumin (BSA) for 4 h

Summary

Introduction

We investigated the effect of 3-iodothyronamine (T1AM) on thermogenic substrates in brown adipocytes (BAs). 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 analyzed in both cell populations. 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. T1AM activates neuroprotective signaling including the activation of the AKT and PKA signaling [2,3]; it stimulates neuronal plasticity [4,5] and induces central-mediated reduction of body temperature without activating the brown adipose tissue [6,7,8]. Most of the pharmacological effects of T1AM, including the effect on body temperature, have been described following acute administration of the amine

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