title: Plasma and liver lipid profiles in rats exposed to chronic hypobaric hypoxia: changes in metabolic pathways.
abstract: Lipid metabolism under chronic hypoxia (CH) has not received equal attention as intermittent hypoxia (IH). To determine the CH-induced changes in plasma and liver, as well as the mRNA and protein expression of two key enzymes in the triglyceride and cholesterol biosynthesis pathways, SREBP-1 (HMG-CoA reductase) and SREBP-2 (SCD-1), we exposed adult male Wistar rats to CH (4600 m; n=15) for 30 days compared to normoxic rats (n=15). The CH rats exhibited weight loss (p<0.001), higher hematocrit (%), and higher hemoglobin (g/dL) (p<0.01). In the plasma of CH rats, total cholesterol and LDL-cholesterol increased at day 15. VLDL-cholesterol and triglycerides (p<0.01) greatly increased (35%), while HDL-cholesterol decreased (p<0.01). Triglycerides and VLDL-cholesterol remained elevated by 28% at day 30 (p<0.01). Hepatic triglycerides increased two-fold, while total cholesterol increased by 51% (p<0.001; p<0.05). Upregulation of SCD-1 mRNA and protein was observed in the CH rats (p<0.01); however, no differences were observed in HMG-CoA reductase mRNA or protein expression in both groups. In conclusion, CH, like IH, alters lipid profiles by increasing triglycerides in the plasma and liver and upregulating triglyceride biosynthesis without affecting the cholesterol biosynthetic pathway. Additional involved mechanisms require further study because of the importance of lipids in cardiovascular risk.
authors.affiliation: 1 Institute of Health Studies. Universidad Arturo Prat , Iquique, Chile .
authors.forename: Patricia
authors.initials: P
authors.lastname: Siques
authors.forename: Julio
authors.initials: J
authors.lastname: Brito
authors.forename: Nelson
authors.initials: N
authors.lastname: Naveas
authors.forename: Ruth
authors.initials: R
authors.lastname: Pulido
authors.forename: Juan José
authors.initials: JJ
authors.lastname: De la Cruz
authors.forename: Maribel
authors.initials: M
authors.lastname: Mamani
authors.forename: Fabiola
authors.initials: F
authors.lastname: León-Velarde
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002784:Cholesterol / Q000378:metabolism*; D002908:Chronic Disease; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D000860:Hypoxia / Q000209:etiology / Q000378:metabolism*; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013230:Stearoyl-CoA Desaturase / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D006454:Hemoglobins; D014280:Triglycerides; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D013230:Stearoyl-CoA Desaturase; C000594769:stearoyl-CoA desaturase SCD-1, rat
keywords: HMG-CoA reductase; SCD-1; blood lipids; chronic hypoxia; high altitude