scholarly journals Effect of Liothyronine Treatment on Dermal Temperature and Activation of Brown Adipose Tissue in Female Hypothyroid Patients: A Randomized Crossover Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Betty Ann Bjerkreim ◽  
Sara Salehi Hammerstad ◽  
Hanne Løvdal Gulseth ◽  
Tore Julsrud Berg ◽  
Sindre Lee-Ødegård ◽  
...  

BackgroundThyroid hormones are essential for the full thermogenic response of brown adipose tissue (BAT) and have been implicated in dermal temperature regulation. Nevertheless, persistent cold-intolerance exists among a substantial proportion of hypothyroid patients on adequate levothyroxine (LT4) substitution.Materials and MethodsTo assess if skin temperature and activation of BAT during treatment with liothyronine (LT3) differs from that of LT4 treatment, fifty-nine female hypothyroid patients with residual symptoms on LT4 or LT4/LT3 combination therapy were randomly assigned in a non-blinded crossover study to receive monotherapy with LT4 or LT3 for 12 weeks each. Change in supraclavicular (SCV) skin temperature overlying BAT, and sternal skin temperature not overlying BAT, during rest and cold stimulation were assessed by infrared thermography (IRT). In addition, abundance of exosomal miR-92a, a biomarker of BAT activation, was estimated as a secondary outcome.ResultsCold stimulated skin temperatures decreased less with LT3 vs. LT4 in both SCV (mean 0.009°C/min [95% CI: 0.004, 0.014]; P<0.001) and sternal areas (mean 0.014°C/min [95% CI: 0.008, 0.020]; P<0.001). No difference in serum exosomal miR-92a abundance was observed between the two treatment groupsConclusionLT3 may reduce dermal heat loss. Thermography data suggested increased BAT activation in hypothyroid patients with cold-intolerance. However, this finding was not corroborated by assessment of the microRNA biomarker of BAT activation.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT03627611

SLEEP ◽  
2019 ◽  
Vol 42 (12) ◽  
Author(s):  
Francisco M Acosta ◽  
Guillermo Sanchez-Delgado ◽  
Borja Martinez-Tellez ◽  
Jairo H Migueles ◽  
Francisco J Amaro-Gahete ◽  
...  

Abstract Study Objectives Short sleep duration and sleep disturbances have been related to obesity and metabolic disruption. However, the behavioral and physiological mechanisms linking sleep and alterations in energy balance and metabolism are incompletely understood. In rodents, sleep regulation is closely related to appropriate brown adipose tissue (BAT) thermogenic activity, but whether the same is true in humans has remained unknown. The present work examines whether sleep duration and quality are related to BAT volume and activity (measured by 18F-FDG) and BAT radiodensity in humans. Methods A total of 118 healthy adults (69% women, 21.9 ± 2.2 years, body mass index: 24.9 ± 4.7 kg/m2) participated in this cross-sectional study. Sleep duration and other sleep variables were measured using a wrist-worn accelerometer for seven consecutive days for 24 hours per day. The Pittsburgh Sleep Quality Index was used to assess sleep quality. All participants then underwent a personalized cold exposure to determine their BAT volume, activity, and radiodensity (a proxy of the intracellular triglyceride content), using static positron emission tomography combined with computed tomography (PET/CI) scan. Results Neither sleep duration nor quality was associated with BAT volume or activity (the latter represented by the mean and peak standardized 18F-FDG uptake values) or radiodensity (all p > .1). The lack of association remained after adjusting the analyses for sex, date of PET/CT, and body composition. Conclusions Although experiments in rodent models indicate a strong relationship to exist between sleep regulation and BAT function, it seems that sleep duration and quality may not be directly related to the BAT variables examined in the present work. Clinical Trial Registration NCT02365129 (ClinicalTrials.gov).


2019 ◽  
Vol 82 ◽  
pp. 178-185 ◽  
Author(s):  
Borja Martinez-Tellez ◽  
Yolanda Garcia-Rivero ◽  
Guillermo Sanchez-Delgado ◽  
Huiwen Xu ◽  
Francisco J. Amaro-Gahete ◽  
...  

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Valentina Hartwig ◽  
Letizia Guiducci ◽  
Martina Marinelli ◽  
Laura Pistoia ◽  
Tommaso Minutoli Tegrimi ◽  
...  

Purpose. A clear link between obesity and brown adipose tissue (BAT) dysfunction has been recently demonstrated. The purpose of this pilot study is to determine if near-infrared spectroscopy (NIRS) 2D imaging together with infrared thermography (IRT) is capable of identifying thermal and vascular response in the supraclavicular (SCV) areas after the ingestion of an oral glucose load as a thermogenic stimulation. Method. We studied two groups of women (obese versus lean) for discerning their different responses. NIRS and IRT images were acquired on the neck in the left SCV region during a 3 h oral glucose tolerance test (OGTT) and immediately after a cold stimulation. Results. We detected a significant thermal response of BAT in SCV fossa in both groups. Both during OGTT and after cold stimulation, skin temperature was persistently higher in lean versus obese. This response was not coupled with changes in oxygen saturation of subcutaneous tissue in that area. Discussion and Conclusion. The results show that NIRS/IRT may be a novel, noninvasive, radiation-free, easy to use, and low-cost method for monitoring, during the standard clinical practice, the diet and pharmacological intervention which aims to stimulate BAT as a potential therapeutic target against obesity and diabetes.


2002 ◽  
Vol 282 (2) ◽  
pp. R623-R626 ◽  
Author(s):  
Kazue Kikuchi-Utsumi ◽  
Bihu Gao ◽  
Hiroshi Ohinata ◽  
Masaaki Hashimoto ◽  
Noriyuki Yamamoto ◽  
...  

It has been shown that norepinephrine (NE) can mediate vasodilatation by stimulating the production of nitric oxide (NO) in brown adipose tissue (BAT), resulting in an increase in BAT blood flow. We speculated that constitutive NO synthase (NOS) is involved in this NO production. However, it is not known whether constitutive NOS is expressed in BAT. To answer this question, we assessed the expression of two types of constitutive NOS, endothelial (eNOS) and neuronal NOS (nNOS), in BAT of rats. eNOS was abundantly expressed in both BAT and isolated brown adipocytes, whereas nNOS was not. Cold exposure, which is known to stimulate NE release from sympathetic nerve terminals in BAT, led to a significant increase in eNOS mRNA in this tissue. In contrast, very low levels of inducible NOS (iNOS) mRNA were expressed, and cold stimulation failed to increase iNOS mRNA levels in BAT. These results suggest that eNOS is the primary isoform that is responsible for NO production in BAT and that its expression may be under sympathetic control.


2021 ◽  
Author(s):  
Xi Cao ◽  
Tingting Shi ◽  
Chuanhai Zhang ◽  
Wanzhu Jin ◽  
Lini Song ◽  
...  

Identification of key regulators of energy homeostasis holds important therapeutic promise for metabolic disorders, such as obesity and diabetes. ACE2 cleaves angiotensin II (Ang II) to generate Ang-(1-7) which acts mainly through the Mas receptor. Here, we identify ACE2 pathway as a critical regulator in the maintenance of thermogenesis and energy expenditure. We found that ACE2 is highly expressed in brown adipose tissue (BAT) and that cold stimulation increases ACE2 and Ang-(1-7) levels in BAT and serum. ACE2 knockout mice (ACE2-/y), Mas knockout mice (Mas-/-), and the mice transplanted with brown adipose tissue from Mas-/- mice displayed impaired thermogenesis. In contrast, impaired thermogenesis of db/db obese diabetic mice and high-fat diet-induced obese mice were ameliorated by overexpression of ACE2 or continuous infusion of Ang-(1-7). Activation of ACE2 pathway was associated with improvement of metabolic parameters, including blood glucose, lipids and energy expenditure in multiple animal models. Consistently, ACE2 pathway remarkably enhanced the browning of white adipose tissue. Mechanistically, we showed that ACE2 pathway activated Akt/FoxO1 and PKA pathway, leading to induction of UCP1 and activation of mitochondrial function. Our data propose that adaptive thermogenesis requires regulation of ACE2 pathway and highlight novel therapeutic targets for the treatment of metabolic disorders.


2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Alexandra Mellerowicz ◽  
Madelene Ericsson ◽  
Mattias Hedlund ◽  
Stefan K Nilsson

Background: Brown adipose tissue (BAT) has a unique to ability to use excess energy for heat production. It is therefore an attractive target organ for counteracting obesity and related metabolic diseases where overfeeding is an underlying cause. BAT has in murine models been shown to clear postprandial lipids quickly. The postprandial response is associated to systemic inflammatory alterations and an increased lipid pressure possibly driving atherosclerosis development. We hypothesized that BAT activation would affect postprandial lipid clearance and that this would reflect in an altered immune cell response. Methods: Young male volunteers were subject to an oral fat tolerance test at two separate occasions during both cold stimulation and in thermoneutral control conditions. Body temperature and EMG activity was monitored and energy expenditure (EE) was measured. Blood samples were taken at baseline and every 30 min for 2 h. Plasma lipids and the immune cell response. Results: Cold stimulation during OFTT resulted in a 19,4 % higher EE compared to warm conditions (P=0,007). Surprisingly, no changes in plasma TG were observed. A 2-fold elevation in free fatty acids (FFA) was seen in cold which also correlated positively with EE (P=0,008). Total plasma cholesterol increased compared to warm conditions by 0,56 mmol/L (P=0,050). LDL-c and HDL-c were increased in cold (0,20 mmol/L difference P=0,048 and 0,16 mmol/L P=0,002) whereas remnant-c was unaltered between the two thermal conditions. White blood cell count (WBC) after OFTT was significantly increased in cold (P = 0,018) by 0,29 х 109/L. Discussion: BAT activation in the postprandial state results in increased HDL-c, possibly indicating increased vascular lipolysis and associated pre-β HDL particle formation. Increased VLDL production due to elevated FFA levels in the cold state and might explain why plasma TG is unaltered and also why LDL-c remains at a higher concentration in the cold. Conclusions: BAT might be an attractive target for obesity treatment but potentially displays pro-atherogenic properties that must be addressed in longitudinal studies.


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