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Control of metabolism in brown adipose tissue
Author(s) -
Williamson John R.,
Prusiner Stanley,
Olson Merle S.,
Fukami Miriam
Publication year - 1970
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/bf02531087
Subject(s) - oligomycin , brown adipose tissue , oxidative phosphorylation , mitochondrion , respiration , biochemistry , beta oxidation , adenine nucleotide , adenosine triphosphate , chemistry , biology , fatty acid , adipose tissue , nucleotide , enzyme , atpase , botany , gene
Cells and mitochondria were isolated from brown adipose tissue of the adult hamster. Isolated mitochondria did not show respiratory control. Reversed electron transport was demonstrated and the oxidation rates of various substrates were compared. α‐Glycerophosphate gave the highest oxidative rate with isolated mitochondria. The low basal respiration of isolated brown fat cells could be stimulated by catecholamines, oleate, succinate, a ‐glycerol phosphate and uncoupling agents. Only norepinephrine or oleate induced respiration was sensitive to inhibition by oligomycin, but this inhibition could not be released by uncoupling agents. Neither atractyloside nor (+) decanoylcarnitine were found to affect respiration, suggesting that mitochondrial nucleotide exchange is slow and that fatty acid oxidation might be carnitine independent. In resting brown fat cells, ATP amounts to 75% of the total adenine nucleotides. NE or oleate caused a small decrease of ATP and a corresponding increase of ADP. Oligomycin caused a partial depletion of ATP content, but subsequent NE addition increased ATP back to control values. This effect was abolished by arsenite. Similarly, uncoupling agents diminished the ATP level which was increased only slightly by NE. Arsenite alone decreased ATP levels to a small extent but a rapid depletion occurred upon subsequent NE addition while respiration was inhibited. Thus, substrate level phosphorylation may be the major energy producing reaction for the generation of ATP and GTP for the activation of fatty acids. Norepinephrine addition to brown fat cells caused an oxidation of pyridine nucleotides, a reduction of flavoproteins and an oxidation of cytochrome b. In constras, succinate produced a reduction of all the components of the respiratory chain. The bioenergetic basis of thermogenesis in brown fat is its high respiratory rate. The rapid respiration induced by norepinephrine or fatty acids appears to be characterized by a low yeild of ATP from oxidative phosphorylation and may be controlled by fatty acid mediated release of energy coupling, possibly by an indirect mechanism.