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Decreased mitochondrial oxidation of fatty acids in pregnant mice: Possible relevance to development of acute fatty liver of pregnancy
Author(s) -
Grimbert Sylvie,
Fromenty Bernard,
Fisch Cecile,
Letteron Philippe,
Berson Alain,
DurandSchneider Anne Marie,
Feldmann Gerard,
Pessayre Dominique
Publication year - 1993
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840170417
Subject(s) - palmitic acid , acute fatty liver of pregnancy , exhalation , fatty acid , beta oxidation , medicine , steatosis , endocrinology , gestation , chemistry , pregnancy , metabolism , biochemistry , biology , anesthesia , genetics
Severe impairment of the β‐oxidation of fatty acids, as a consequence of a single factor or a combination of different causes, leads to microvesicular steatosis of the liver. In an effort to understand the mechanism(s) leading to the development of acute fatty liver of pregnancy in some women, we determined the effects of pregnancy on the mitochondrial oxidation of fatty acids in mice. In vivo , the rate of oxidation of the whole fatty‐acid chain length was determined by measuring the rate of exhalation of [ 14 C]CO 2 after intragastric administration of a tracer dose of [U‐ 14 C]palmitic acid. [ 14 C]CO 2 exhalation was not significantly decreased at 14 days of gestation, but it had declined by 40% at 18 days of gestation (i.e., 24 to 48 hr before delivery). The rate of first β‐oxidation cycle was assessed by measuring the rate of [ 14 C]CO 2 exhalation after administration of [1‐ 14 C]octanoic acid, [1‐ 14 C]butyric acid or [1‐ 14 C]palmitic acid. [ 14 C]CO 2 exhalation had declined by 60%, 46%, and 24% after administration of [1‐ 14 C]octanoic acid, [1‐ 14 C]butyric acid and [1‐ 14 C]palmitic acid, respectively, in 18‐day‐pregnant mice. Total hepatic lipids and triglycerides, expressed per gram of liver, remained unchanged in 18‐day‐pregnant mice. In vitro , the rate of mitochondrial β‐oxidation (expressed per milligram of protein) had decreased by 47% at 18 days' gestation with [U‐ 14 C]palmitic acid as substrate and by 33% with [1‐ 14 C]octanoic acid but remained unchanged with [1‐ 14 C]palmitic acid. The activity of the tricarboxylic acid cycle, assessed by the formation of [ 14 C]CO 2 from [1‐ 14 C]acetic acid, had decreased by 24%. We conclude that the mitochondrial oxidation of fatty acids decreased during late‐term pregnancy in mice as a consequence of both decreased mitochondrial β‐oxidation of medium‐chain fatty acids, and decreased activity of the tricarboxylic acid cycle. We suggest that this effect, in combination with other factors, may contribute to the development of fatty liver of pregnancy in some pregnant women. (H EPATOLOGY 1993;17:628–637.)