scholarly journals N- and O-Acetylated 3-Iodothyronamines Have No Metabolic or Thermogenic Effects in Male Mice

2019 ◽  
Vol 9 (2) ◽  
pp. 57-66
Author(s):  
Sogol Gachkar ◽  
Rebecca Oelkrug ◽  
Beate Herrmann ◽  
Thomas S. Scanlan ◽  
Qian Sun ◽  
...  

Introduction: Injection of 3-iodothyronamine into experimental animals profoundly affects their metabolism and body temperature. As 3-iodothyronamine is rapidly acetylated in vivo after injection, it was hypothesized that the metabolites N- or O-acetyl-3-iodothyronamines could constitute the active hormones. Methods: Adult male mice were injected once daily with one of the metabolites (5 mg/kg body weight intraperitoneally dissolved in 60% DMSO in PBS) or solvent. Metabolism was monitored by indirect calorimetry, body temperature by infrared thermography, and body composition by nuclear magnetic resonance analysis. Signaling activities in brown fat or liver were assessed by studying target gene transcription by qPCR including uncoupling protein 1 or deiodinase type 1 or 2, and Western blot. Results: The markers of metabolism, body composition, or temperature tested were similar in the mice injected with solvent and those injected with one of the acetylated 3-iodothyronamines. Conclusions: In our experimental setup, N- and O-acetyl-3-iodothyronamine do not constitute compounds contributing to the metabolic or temperature effects described for 3-iodothyronamine. The acetylation of 3-iodothyronamine observed in vivo may thus rather serve degradation and elimination purposes.

2021 ◽  
Author(s):  
Marta Lantero Rodriguez ◽  
Maaike Schilperoort ◽  
Inger Johansson ◽  
Elin Svedlund Eriksson ◽  
Vilborg Palsdottir ◽  
...  

Brown adipose tissue (BAT) burns substantial amounts of mainly lipids to produce heat. Some studies indicate that BAT activity and core body temperature are lower in males than females. Here we investigated the role of testosterone and its receptor (the androgen receptor; AR) in metabolic BAT activity in male mice. Castration, which renders mice testosterone deficient, slightly promoted the expression of thermogenic markers in BAT, decreased BAT lipid content, and increased basal lipolysis in isolated brown adipocytes. Further, castration increased the core body temperature. Triglyceride-derived fatty acid uptake, a proxy for metabolic BAT activity in vivo, was strongly increased in BAT from castrated mice (4.5-fold increase vs. sham-castrated mice) and testosterone replacement reversed the castration-induced increase in metabolic BAT activity. BAT-specific AR deficiency did not mimic the castration effects in vivo and AR agonist treatment did not diminish the activity of cultured brown adipocytes in vitro, suggesting that androgens do not modulate BAT activity via a direct, AR-mediated pathway. In conclusion, testosterone is a negative regulator of metabolic BAT activity in male mice. Our findings provide new insight into the metabolic actions of testosterone.


2012 ◽  
Vol 302 (1) ◽  
pp. R118-R125 ◽  
Author(s):  
Naoya Kitao ◽  
Masaaki Hashimoto

Brown adipose tissue (BAT) is thought to play a significant physiological role during arousal when body temperature rises from the extremely low body temperature that occurs during hibernation. The dominant pathway of BAT thermogenesis occurs through the β3-adrenergic receptor. In this study, we investigated the role of the β3-adrenergic system in BAT thermogenesis during arousal from hibernation both in vitro and in vivo. Syrian hamsters in the hibernation group contained BAT that was significantly greater in overall mass, total protein, and thermogenic uncoupling protein-1 than BAT from the warm-acclimated group. Although the ability of the β3-agonist CL316,243 to induce BAT thermogenesis at 36°C was no different between the hibernation and warm-acclimated groups, its maximum ratio over the basal value at 12°C in the hibernation group was significantly larger than that in the warm-acclimated group. Forskolin stimulation at 12°C produced equivalent BAT responses in these two groups. In vivo thermogenesis was assessed with the arousal time determined by the time course of BAT temperature or heart rate. Stimulation of BAT by CL316,243 significantly shortened the time of arousal from hibernation compared with that induced by vehicle alone, and it also induced arousal in deep hibernating animals. The β3-antagonist SR59230A inhibited arousal from hibernation either in part or completely. These results suggest that BAT in hibernating animals has potent thermogenic activity with a highly effective β3-receptor mechanism at lower temperatures.


2008 ◽  
Vol 74 (22) ◽  
pp. 6908-6917 ◽  
Author(s):  
Pyung Cheon Lee ◽  
Christine Salomon ◽  
Benjamin Mijts ◽  
Claudia Schmidt-Dannert

ABSTRACT Enzymatic steps from two different biosynthetic pathways were combined in Escherichia coli, directing the synthesis of a new class of biomolecules—ubiquinones with prenyl side chains containing conjugated double bonds. This was achieved by the activity of a C30 carotenoid desaturase, CrtN, from Staphylococcus aureus, which exhibited an inherent flexibility in substrate recognition compared to other carotenoid desaturases. By utilizing the known plasticity of E. coli's native ubiquinone biosynthesis pathway and the unusual activity of CrtN, modified ubiquinone structures with prenyl side chains containing conjugated double bonds were generated. The side chains of the new structures were confirmed to have different degrees of desaturation by mass spectrometry and nuclear magnetic resonance analysis. In vivo 14C labeling and in vitro activity studies showed that CrtN desaturates octaprenyl diphosphates but not the ubiquinone compounds directly. Antioxidant properties of conjugated side chain ubiquinones were analyzed in an in vitro β-carotene-linoleate model system and were found to be higher than the corresponding unmodified ubiquinones. These results demonstrate that by combining pathway steps from different branches of biosynthetic networks, classes of compounds not observed in nature can be synthesized and structural motifs that are functionally important can be combined or enhanced.


2013 ◽  
Vol 80 (4) ◽  
pp. 1421-1429 ◽  
Author(s):  
Manami Hyakutake ◽  
Satoshi Tomizawa ◽  
Kouhei Mizuno ◽  
Hideki Abe ◽  
Takeharu Tsuge

ABSTRACTPolyhydroxyalkanoate (PHA)-producingBacillusstrains express class IV PHA synthase, which is composed of the subunits PhaR and PhaC. RecombinantEscherichia coliexpressing PHA synthase fromBacillus cereusstrain YB-4 (PhaRCYB-4) showed an unusual reduction of the molecular weight of PHA produced during the stationary phase of growth. Nuclear magnetic resonance analysis of the low-molecular-weight PHA revealed that its carboxy end structure was capped by ethanol, suggesting that the molecular weight reduction was the result of alcoholytic cleavage of PHA chains by PhaRCYB-4induced by endogenous ethanol. This scission reaction was also induced by exogenous ethanol in bothin vivoandin vitroassays. In addition, PhaRCYB-4was observed to have alcoholysis activity for PHA chains synthesized by other synthases. The PHA synthase fromBacillus megaterium(PhaRCBm) from another subgroup of class IV synthases was also assayed and was shown to have weak alcoholysis activity for PHA chains. These results suggest that class IV synthases may commonly share alcoholysis activity as an inherent feature.


2011 ◽  
pp. 65-73 ◽  
Author(s):  
F. C. HOWARTH ◽  
M. JACOBSON ◽  
M. SHAFIULLAH ◽  
M. LJUBISAVLJEVIC ◽  
E. ADEGHATE

Diabetes mellitus is associated with a variety of cardiovascular complications including impaired cardiac muscle function. The effects of insulin treatment on heart rate, body temperature and physical activity in the alloxan (ALX)-induced diabetic rat were investigated using in vivo biotelemetry techniques. The electrocardiogram, physical activity and body temperature were recorded in vivo with a biotelemetry system for 10 days before ALX treatment, for 20 days following administration of ALX (120 mg/kg) and thereafter, for 15 days whilst rats received daily insulin. Heart rate declined rapidly after administration of ALX. Pre-ALX heart rate was 321±9 beats per minute, falling to 285±12 beats per minute 15-20 days after ALX and recovering to 331±10 beats per minute 5-10 days after commencement of insulin. Heart rate variability declined and PQ, QRS and QT intervals were prolonged after administration of ALX. Physical activity and body temperature declined after administration of ALX. Pre-ALX body temperature was 37.6±0.1 °C, falling to 37.3±0.1 °C 15-20 days after ALX and recovering to 37.8±0.1 °C 5-10 days after commencement insulin. ALX-induced diabetes is associated with disturbances in heart rhythm, physical activity and body temperature that are variously affected during insulin treatment.


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