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Brain pyruvate recycling and peripheral metabolism: an NMR analysis ex vivo of acetate and glucose metabolism in the rat
Author(s) -
Serres Sébastien,
Bezancon Eric,
Franconi JeanMichel,
Merle Michel
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04442.x
Subject(s) - gluconeogenesis , metabolism , glutamate receptor , carbohydrate metabolism , chemistry , endocrinology , medicine , metabolite , pyruvic acid , biochemistry , biology , receptor
The occurrence of pyruvate recycling in the rat brain was studied in either pentobarbital anesthetized animals or awake animals receiving a light analgesic dose of morphine, which were infused with either [1‐ 13 C]glucose + acetate or glucose + [2‐ 13 C]acetate for various periods of time. Metabolite enrichments in the brain, blood and the liver were determined from NMR analyses of tissue extracts. They indicated that: (i) Pyruvate recycling was revealed in the brain of both the anesthetized and awake animals, as well as from lactate and alanine enrichments as from glutamate isotopomer composition, but only after infusion of glucose + [2‐ 13 C]acetate. (ii) Brain glucose was labelled from [2‐ 13 C]acetate at the same level in anaesthetized and awake rats (∼4%). Comparing its enrichment with that of blood and liver glucose indicated that brain glucose labelling resulted from hepatic gluconeogenesis. (iii) Analysing glucose 13 C‐ 13 C coupling in the brain, blood and the liver confirmed that brain glucose could be labelled in the liver through the activities of both pyruvate recycling and gluconeogenesis. (iv) The rate of appearance and the amount of brain glutamate C4–C5 coupling, a marker of pyruvate recycling when starting from [2‐ 13 C]acetate, were lower than those of brain glucose labelling from hepatic metabolism. (v) The evaluation of the contributions of glucose and acetate to glutamate metabolism revealed that more than 60% of brain glutamate was synthesized from glucose whereas only 7% was from acetate and that glutamate C4–C5 coupling was mainly due to the metabolism of glucose labelled through hepatic gluconeogenesis. All these results indicate that, under the present conditions, the pyruvate recycling observed through the labelling of brain metabolites mainly originates from peripheral metabolism.