title: Decreased mitochondrial oxidation of fatty acids in pregnant mice: possible relevance to development of acute fatty liver of pregnancy.
abstract: Severe impairment of the beta-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 [14C]CO2 after intragastric administration of a tracer dose of [U-14C]palmitic acid. [14C]CO2 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 beta-oxidation cycle was assessed by measuring the rate of [14C]CO2 exhalation after administration of [1-14C]octanoic acid, [1-14C]butyric acid or [1-14C]palmitic acid. [14C]CO2 exhalation had declined by 60%, 46%, and 24% after administration of [1-14C]octanoic acid, [1-14C]butyric acid and [1-14C]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 beta-oxidation (expressed per milligram of protein) had decreased by 47% at 18 days' gestation with [U-14C]palmitic acid as substrate and by 33% with [1-14C]octanoic acid but remained unchanged with [1-14C]palmitic acid. The activity of the tricarboxylic acid cycle, assessed by the formation of [14C]CO2 from [1-14C]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 beta-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.
authors: Unité de Recherches de Physiopathologie Hépatique (Institut National de la Santé et de la Recherche Médicale Unité 24, Hôpital Beaujon, Clichy, France.
authors: S
authors: S
authors: Grimbert
authors: B
authors: B
authors: Fromenty
authors: C
authors: C
authors: Fisch
authors: P
authors: P
authors: Letteron
authors: A
authors: A
authors: Berson
authors: A M
authors: AM
authors: Durand-Schneider
authors: G
authors: G
authors: Feldmann
authors: D
authors: D
authors: Pessayre
mesh_terms: D042964:Acyl-CoA Dehydrogenase; D000818:Animals; D001835:Body Weight; D002250:Carbon Radioisotopes; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D003066:Coenzyme A Ligases / Q000378:metabolism; D044943:Fatty Acid Desaturases / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005234:Fatty Liver / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D007527:Isoenzymes / Q000378:metabolism; D008099:Liver / Q000033:anatomy & histology / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008854:Microscopy, Electron; D008930:Mitochondria, Liver / Q000378:metabolism* / Q000648:ultrastructure; D009929:Organ Size; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism / Q000503:physiopathology*; D011270:Pregnancy, Animal / Q000378:metabolism*; D011865:Radioisotope Dilution Technique; D012016:Reference Values; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
chemical_list: D002250:Carbon Radioisotopes; D005230:Fatty Acids, Nonesterified; D007527:Isoenzymes; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D044943:Fatty Acid Desaturases; D042964:Acyl-CoA Dehydrogenase; D002334:Carnitine O-Palmitoyltransferase; D003066:Coenzyme A Ligases; C090799:FAA2 protein, S cerevisiae; D000098859:Long-Chain-Fatty-Acid-CoA Ligase