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Effect of deficiency in SREBP cleavage-activating protein on lipid metabolism during intermittent hypoxia


, : Effect of deficiency in SREBP cleavage-activating protein on lipid metabolism during intermittent hypoxia. Physiological Genomics 31(2): 273-280

Obstructive sleep apnea (OSA), a condition leading to intermittent hypoxia (IH) during sleep, has been associated with dyslipidemia, atherosclerosis, and increased cardiovascular mortality. We previously showed in C57BL/6J mice that IH causes hypercholesterolemia and upregulation of sterol regulatory element binding protein ( SREBP)-1, a transcription factor of lipid biosynthesis in the liver. The goal of the present study was to provide mechanistic evidence that IH causes hypercholesterolemia via the SREBP-1 pathway. We utilized mice with a conditional knockout of SREBP cleavage-activating protein (SCAP) in the liver (L-Scap - mice), which exhibit low levels of an active nuclear isoform of SREBP-1 ( nSREBP-1). We exposed L- Scap - mice and wild- type (WT) littermates to IH or intermittent air control for 5 days. IH was induced during the 12-h light phase by decreasing FIO2 from 20.9% to 5% for a period of 30 s with rapid reoxygenation to 20.9% through the subsequent 30 s. In WT mice, IH increased fasting levels of serum total and HDL cholesterol, serum triglycerides, serum and liver phospholipids, mRNA levels of SREBP-1 and mitochondrial glycerol- 3- phosphate acyltransferase (mtGPAT), and protein levels of SCAP, nSREBP-1, and mtGPAT in the liver. In L- Scap - mice, IH did not have any effect on serum and liver lipids, and expression of lipid metabolic genes was not altered. We conclude that hyperlipidemia in response to IH is mediated via the SREBP-1 pathway. Our data suggest that the SREBP-1 pathway could be used as a therapeutic target in patients with both OSA and hyperlipidemia.

US$19.90

PMID: 17666524

DOI: 10.1152/physiolgenomics.00082.2007


Other references

Sweeney, S.S., 1980: OR observations: key to postop pain. Aorn Journal 32(3): 391-400

Pollastro Richard M., 1999: Application of the total petroleum system concept to assessing undiscovered gas resources of the Ghaba and Fahud salt basin provinces, north-central Oman. The U.S Geological Survey, World Energy Project, ranked the Ghaba and Fahud Salt Basin Provinces of Oman as "priority" global geologic provinces on the basis of discovered petroleum volumes. The Total Petroleum System concept, modified f...

Schott L., 1974: Criticism of the phase doctrine of ontogenetic development in childhood and adolescence. Biologische Rundschau 12(5): 341-345

Svensson, Mats E., 2004: Gene duplication and evolutionary novelties Studies on plants and vertebrates. Journal of Morphology 260(3): 333, June

Mayberry, J.F., 1979: The history of a hospital and its diagnostic index. Public Health 93(5): 311-316

Csaba, B.; Szilagyi, T.; Kavai, M.; Szatai, I.; Toth, F., 1961: The effect of x-rays on anaphylaxis in the guinea pig. About 50% of male guinea pigs sensitized with 5 mg ovalbumin 7 days after whole-body irradiation with 200 r survived anaphylactic shock, whereas all nonirradiated controls died within 4 minutes after reinjection. Irradiation had no effect on the r...

Edmunds, L.J.; Sulzman, F.; Walther, W., 1974: Circadian oscillations in enzyme activity in Euglena and their relation to the circadian rhythm of cell division. Chronobiology L E Scheving F Halberg and J E Paulyeds: 1-66

Leng, P.; Yamamura, H., 2006: Fruit set and embryo rescue in crosses using parthenocarpic 'Mopanshi' persimmon. The 'Mopanshi' persimmon is a seedless, astringent parthenocarpic cultivar that does not produce male flowers. After pollination using four non-astringent cultivars ('Zenjimaru', 'Nishimurawase', 'Okugosho'...

Bresson, D.; von Herrath, M., 2007: Limitations in immunotherapy with CD3 antibodies: comment on the article by Drs. Chatenoud and Bach. Review of Diabetic Studies 2(4): 187-9; Discussion 190-1

Snásil, M.; Nĕmecek, L.; Mezerová, J., 1991: Evaluation of Elevent, a ventilator manufactured in Czechoslovakia for controlled ventilation during inhalation anesthesia in dogs. Controlled breathing during halothane inhalation anesthesia was tested experimentally in fifty clinically healthy test dogs. In the first group the breathing regime was evaluated when a new Czechoslovak electronic ventilator Elvent was used in the...