Studies on the energy state of isolated brown adipose tissue mitochondria. Effect of adenine nucleotides and oligomycin on the generation and dissipation of the “energy potential”

During norepinephrine (NE) induced thermogenesis in the adipocytes of brown adipose tissue (BAT), the blood flow of the tissue, and thus its oxygen supply, seems to be controlled by the adipocytes, possibly through their production of a vasodilator. This study sought to discover a metabolic parameter of the adipocytes that might account for modulation of vasodilator production and BAT blood flow. The blood flow of the interscapular BAT (IBAT) of anesthetized, cold-acclimated rats was varied by infusing NE and by altering the concentration of oxygen in arterial blood [Formula: see text]. Flow was measured with radiolabeled microspheres. IBAT was freeze fixed in situ for determination of its levels of adenine nucleotides and its cytosolic redox state; the latter was measured in terms of the concentration ratios, lactate/pyruvate (L/P) and glycerol-3-phosphate/dihydroxy-acetone phosphate (GP/DHAP) in the tissue. The increase in IBAT blood flow with dose of NE was associated with a progressive decline in tissue ATP, increases in ADP and AMP at high doses of NE, and progressive increases in L/P and GP/DHAP, the latter increases indicating increased reduction of the cytosolic NAD+–NADH system. Reducing [Formula: see text] by hemodilution raised the blood flow, L/P, and GP/DHAP of IBAT to values significantly above those measured in rats of normal [Formula: see text] given the same doses of NE; whereas, elevating [Formula: see text] by hemoconcentration had the opposite effects on these values. For rats of normal or altered [Formula: see text] together, a correlation coefficient of 0.94 was obtained for the relation between IBAT blood flow and L/P and one of 0.85 for that between flow and GP/DHAP. The coefficients for these relations were 0.98 when data from rats of normal [Formula: see text] only were used. Changes in the levels of ATP, ADP, and AMP or in the ratios of these nucleotides in IBAT did not correspond well with changes in blood flow. The results indicate that the cytosolic redox state of BAT may be the metabolic parameter underlying the control of BAT blood flow.

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Guanosine-diphosphate causing changes in the phosphorylation pattern of adenine nucleotides in mitochondria from brown adipose tissue

FEBS Letters ◽

10.1016/0014-5793(72)80692-6 ◽

1972 ◽

Vol 28 (2) ◽

pp. 125-128 ◽

Cited By ~ 16

Author(s):

J. Rafael ◽

H.W. Heldt ◽

H.-J. Hohorst

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Adenine Nucleotides ◽

Guanosine Diphosphate ◽

Brown Adipose ◽

Phosphorylation Pattern

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Functional characterization of human brown adipose tissue metabolism

Biochemical Journal ◽

10.1042/bcj20190464 ◽

2020 ◽

Vol 477 (7) ◽

pp. 1261-1286 ◽

Cited By ~ 3

Author(s):

Marie Anne Richard ◽

Hannah Pallubinsky ◽

Denis P. Blondin

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Functional Characterization ◽

Human Infants ◽

Positron Emission ◽

Brown Adipose ◽

Treatment Of Obesity ◽

And Function

Brown adipose tissue (BAT) has long been described according to its histological features as a multilocular, lipid-containing tissue, light brown in color, that is also responsive to the cold and found especially in hibernating mammals and human infants. Its presence in both hibernators and human infants, combined with its function as a heat-generating organ, raised many questions about its role in humans. Early characterizations of the tissue in humans focused on its progressive atrophy with age and its apparent importance for cold-exposed workers. However, the use of positron emission tomography (PET) with the glucose tracer [18F]fluorodeoxyglucose ([18F]FDG) made it possible to begin characterizing the possible function of BAT in adult humans, and whether it could play a role in the prevention or treatment of obesity and type 2 diabetes (T2D). This review focuses on the in vivo functional characterization of human BAT, the methodological approaches applied to examine these features and addresses critical gaps that remain in moving the field forward. Specifically, we describe the anatomical and biomolecular features of human BAT, the modalities and applications of non-invasive tools such as PET and magnetic resonance imaging coupled with spectroscopy (MRI/MRS) to study BAT morphology and function in vivo, and finally describe the functional characteristics of human BAT that have only been possible through the development and application of such tools.

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