title: Selective regulation of hepatic lipid metabolism by the AMP-activated protein kinase pathway in late-pregnant rats.
abstract: The liver plays an essential role in maternal metabolic adaptation during late pregnancy. With regard to lipid metabolism, increased secretion of very low-density lipoprotein (VLDL) is characteristic of late pregnancy. Despite this well-described metabolic plasticity, the molecular changes underlying the hepatic adaptation to pregnancy remain unclear. As AMPK is a key intracellular energy sensor, we investigated whether this protein assumes a causal role in the hepatic adaptation to pregnancy. Pregnant Wistar rats were treated with vehicle or AICAR (5-aminoimidazole-4-carboxamide ribonucleotide) for 5 days starting at gestational day 14. At the end of treatment, the rats were subjected to an intraperitoneal pyruvate tolerance test and in situ liver perfusion with pyruvate. The livers were processed for Western blot analysis, quantitative PCR, thin-layer chromatography, enzymatic activity, and glycogen content measurements. Blood biochemical profiles were also assessed. We found that AMPK and ACC phosphorylation were reduced in the livers of pregnant rats in parallel with a reduced level of hepatic gluconeogenesis of pyruvate. This effect was accompanied by both a reduction in the levels of hepatic triglycerides (TG) and an increase in circulating levels of TG. Treatment with AICAR restored hepatic levels of TG to those observed in nonpregnant rats. Additionally, AMPK activation reduced the upregulation of genes related to VLDL synthesis and secretion observed in the livers of pregnant rats. We conclude that the increased secretion of hepatic TG in late pregnancy is concurrent with a transcriptional profile that favors VLDL production. This transcriptional profile results from the reduction in hepatic AMPK activity.
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil;
authors.forename: Sandra C
authors.initials: SC
authors.lastname: Rodrigues
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil;
authors.forename: Lucas C
authors.initials: LC
authors.lastname: Pantaleão
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil;
authors.forename: Tatiane C
authors.initials: TC
authors.lastname: Nogueira
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil;
authors.forename: Patrícia R
authors.initials: PR
authors.lastname: Gomes
authors.affiliation: School of Education, Sciences, Arts and Humanities, University of Grande Rio, Grande Rio, Brazil;
authors.forename: Gabriela G
authors.initials: GG
authors.lastname: Albuquerque
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil;
authors.forename: Renato T
authors.initials: RT
authors.lastname: Nachbar
authors.affiliation: Department of Biophysics and Physiology, Health Science Center, Federal University of Piauí, Piauí, Brazil;
authors.forename: Francisco L
authors.initials: FL
authors.lastname: Torres-Leal
authors.affiliation: Department of Biological Sciences and.
authors.forename: Luciana C
authors.initials: LC
authors.lastname: Caperuto
authors.affiliation: Institute of Environmental, Chemical and Pharmaceutical Sciences, Federal University of São Paulo, São Paulo, Brazil; and.
authors.forename: Camilo
authors.initials: C
authors.lastname: Lellis-Santos
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, Campinas, Brazil.
authors.forename: Gabriel F
authors.initials: GF
authors.lastname: Anhê
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil; sbordin@icb.usp.br.
authors.forename: Silvana
authors.initials: S
authors.lastname: Bordin
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D005943:Gluconeogenesis / Q000187:drug effects / Q000502:physiology; D006003:Glycogen / Q000737:chemistry / Q000378:metabolism; D050356:Lipid Metabolism / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D008291:Malate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012265:Ribonucleotides / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D012265:Ribonucleotides; D014280:Triglycerides; D000620:Aminoimidazole Carboxamide; D006003:Glycogen; D008291:Malate Dehydrogenase; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide
keywords: AMPK; lipid metabolism; liver; pregnancy; very low-density lipoprotein