scholarly journals Stimulation of Glucose Metabolism in Brown Adipose Tissue by Addition of Insulin in Vitro

1966 ◽  
Vol 241 (17) ◽  
pp. 4004-4010
Author(s):  
Stanley E. Shackney ◽  
Cliffe D. Joel
1968 ◽  
Vol 46 (6) ◽  
pp. 897-902 ◽  
Author(s):  
Barbara A. Horwitz ◽  
Paul A. Herd ◽  
Robert Emrie Smith

Examination of the in vivo effect of 2,4-dinitrophenol (DNP) on the brown adipose tissue of cold-exposed rats, as well as the in vitro response of this tissue to DNP and dicumarol, indicates that brown fat does possess a functional electron transport coupled phosphorylating system. Moreover, the fact that a norepinephrine-induced thermogenic response (in vivo) can be elicited from the brown fat after DNP administration implies that the effect of norepinephrine (NE) is not primarily due either to a physiological uncoupling by fatty acids, the level of which is increased by NE, or to stimulation of an ATP-ase system. Alternatively, our data suggest that under basal conditions (i.e. when the animal is not stimulated by cold stress or NE), the heat production (oxygen consumption) of the brown fat is limited by the availability of substrate rather than ADP. It is thus proposed that the thermogenic effect of NE results from the stimulation of lipolysis and an attendant increase of substrate available for oxidation.


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.


eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Haiying Zhou ◽  
Bo Wan ◽  
Ivan Grubisic ◽  
Tommy Kaplan ◽  
Robert Tjian

Brown adipose tissue (BAT) plays an essential role in metabolic homeostasis by dissipating energy via thermogenesis through uncoupling protein 1 (UCP1). Previously, we reported that the TATA-binding protein associated factor 7L (TAF7L) is an important regulator of white adipose tissue (WAT) differentiation. In this study, we show that TAF7L also serves as a molecular switch between brown fat and muscle lineages in vivo and in vitro. In adipose tissue, TAF7L-containing TFIID complexes associate with PPARγ to mediate DNA looping between distal enhancers and core promoter elements. Our findings suggest that the presence of the tissue-specific TAF7L subunit in TFIID functions to promote long-range chromatin interactions during BAT lineage specification.


1995 ◽  
Vol 20 (6) ◽  
pp. 477-484 ◽  
Author(s):  
Akihiro Kuroshima ◽  
Tomie Ohno ◽  
Mitsuru Moriya ◽  
Hiroshi Ohinata ◽  
Takehiro Yahata ◽  
...  

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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