scholarly journals Systemic  -Adrenergic Stimulation of Thermogenesis Is Not Accompanied by Brown Adipose Tissue Activity in Humans

Diabetes ◽  
2012 ◽  
Vol 61 (12) ◽  
pp. 3106-3113 ◽  
Author(s):  
M. J. Vosselman ◽  
A. A. J. J. van der Lans ◽  
B. Brans ◽  
R. Wierts ◽  
M. A. van Baak ◽  
...  
2018 ◽  
Author(s):  
Essam A. Assali ◽  
Anthony E. Jones ◽  
Michaela Veliova ◽  
Mahmoud Taha ◽  
Nathanael Miller ◽  
...  

AbstractA sharp increase in mitochondrial Ca2+ marks the activation of the brown adipose tissue (BAT) thermogenesis, yet the mechanisms preventing Ca2+ deleterious effects are poorly understood. Here, we show that adrenergic stimulation of BAT activates a PKA-dependent mitochondrial Ca2+ extrusion via the mitochondrial Na+/Ca2+ exchanger, NCLX. Adrenergic stimulation of NCLX-ablated brown adipocytes (BA) induces a profound mitochondrial Ca2+ overload and impaired uncoupled respiration. Core body temperature, PET imaging and VO2 measurements confirm a BAT specific thermogenic defect in NCLX-null mice.We show that mitochondrial Ca2+ overload induced by adrenergic stimulation of NCLX-null BAT, triggers the opening of the mitochondrial permeability transition pore (mPTP), leading to remarkable mitochondrial swelling, Cytochrome c release and cell death in BAT. However, treatment with mPTP inhibitors rescue mitochondrial respiratory function and thermogenesis in NCLX-null BA, in vitro and in vivo.Our findings identify a novel pathway enabling non-lethal mitochondrial Ca2+ elevation during adrenergic stimulation of uncoupled respiration. Deletion of NCLX transforms the adrenergic pathway responsible for the stimulation of thermogenesis into a death pathway.


1995 ◽  
Vol 73 (11) ◽  
pp. 1625-1631 ◽  
Author(s):  
Hugues Oudart ◽  
Christiane Calgari ◽  
Margaret Andriamampandry ◽  
Yvon Le Maho ◽  
André Malan

Despite anorexia, cancer development is frequently accompanied by an increase of energy expenditure. Considering the pivotal role played by brown adipose tissue (BAT) in the energy metabolism of small mammals, we investigated the functional and compositional modification in BAT of anorexic tumor-bearing (Yoshida sarcoma) and pair-fed control rats. BAT thermogenic activity (assessed by maximal mitochondrial GDP binding) was 1.8-fold greater in tumor-bearing rats than in controls, while the thermogenic capacity (assessed by measurement of uncoupling protein) was unchanged. This suggests that tumor bearing had induced an unmasking of uncoupling protein sites. BAT hypertrophy and hyperplasia, characteristic of full-fledged BAT activation, did not occur. The mitochondrial oxidative capacity of BAT (assessed by cytochrome c oxidase activity) was 1.6-fold lower in tumor-bearing than in control rats. The main compositional modification observed in BAT of tumor-bearing rats was an increase in the saturation of cardiolipin fatty acids. These results suggest that the BAT stimulation induced by tumor bearing after 10 days is almost exclusively functional and that the tissue development is limited, probably by anorexia. However, a suppressive effect of anorexia inhibition by tumor bearing cannot be excluded.Key words: cancer cachexia, nonshivering thermogenesis, brown adipose tissue cardiolipins.


2020 ◽  
Author(s):  
Milena Monfort-Pires ◽  
Muuez U-Din ◽  
Guilherme A. Nogueira ◽  
Juliana de Almeida-Faria ◽  
Davi Sidarta-Oliveira ◽  
...  

Metabolism ◽  
2021 ◽  
Vol 117 ◽  
pp. 154709 ◽  
Author(s):  
Tim Hollstein ◽  
Karyne Vinales ◽  
Kong Y. Chen ◽  
Aaron M. Cypess ◽  
Alessio Basolo ◽  
...  

Pain ◽  
2016 ◽  
Vol 157 (11) ◽  
pp. 2561-2570 ◽  
Author(s):  
Elizabeth M. Goudie-DeAngelis ◽  
Ramy E. Abdelhamid ◽  
Myra G. Nunez ◽  
Casey L. Kissel ◽  
Katalin J. Kovács ◽  
...  

1983 ◽  
Vol 245 (6) ◽  
pp. E555-E559 ◽  
Author(s):  
D. Szillat ◽  
L. J. Bukowiecki

Adenosine competitively inhibited the stimulatory effects of (-)-isoproterenol on lipolysis and respiration in hamster brown adipocytes. The low value of the apparent ki for respiratory inhibition by adenosine (7 nM) indicated that the nucleoside may control brown adipocyte function under physiological concentrations. Significantly, the dose-response curves for isoproterenol stimulation of lipolysis and respiration were both shifted by adenosine to higher agonist concentrations by the same order of magnitude, providing additional evidence for a tight coupling between lipolysis and respiration. The inhibitory effects of adenosine were rapidly reversed by a) adenosine deaminase, b) agents known to increase intracellular cyclic AMP levels (isoproterenol, isobutylmethylxanthine, dibutyryl cyclic AMP), and c) direct stimulation of respiration with palmitic acid. These results, combined with the fact that adenosine failed to affect respiration evoked either by dibutyryl cyclic AMP or by palmitic acid, strongly indicate that adenosine regulates brown adipose tissue respiration at an early metabolic step of the stimulus-thermogenesis sequence, most probably at the level of the adenylate cyclase complex.


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