Chronic intermittent hypoxia upregulates genes of lipid biosynthesis in obese mice
- PMID: 16037401
- DOI: 10.1152/japplphysiol.00522.2005
Chronic intermittent hypoxia upregulates genes of lipid biosynthesis in obese mice
Abstract
Obstructive sleep apnea (OSA), a condition tightly linked to obesity, leads to chronic intermittent hypoxia (CIH) during sleep. There is emerging evidence that OSA is independently associated with insulin resistance and fatty liver disease, suggesting that OSA may affect hepatic lipid metabolism. To test this hypothesis, leptin-deficient obese (ob/ob) mice were exposed to CIH during the light phase (9 AM-9 PM) for 12 wk. Liver lipid content and gene expression profile in the liver (Affymetrix 430 GeneChip with real-time PCR validation) were determined on completion of the exposure. CIH caused a 30% increase in triglyceride and phospholipid liver content (P < 0.05), whereas liver cholesterol content was unchanged. Gene expression analysis showed that CIH upregulated multiple genes controlling 1) cholesterol and fatty acid biosynthesis [malic enzyme and acetyl coenzyme A (CoA) synthetase], 2) predominantly fatty acid biosynthesis (acetyl-CoA carboxylase and stearoyl-CoA desaturases 1 and 2), and 3) triglyceride and phospholipid biosynthesis (mitochondrial glycerol-3-phosphate acyltransferase). A majority of overexpressed genes were transcriptionally regulated by sterol regulatory element-binding protein (SREBP) 1, a master regulator of lipogenesis. A 2.8-fold increase in SREBP-1 gene expression in CIH was confirmed by real-time PCR (P = 0.001). Expression of major genes of cholesterol biosynthesis, SREBP-2 and 3-hydroxy-3-methylglutaryl-CoA reductase, was unchanged. In conclusion, we have shown that CIH may exacerbate preexisting fatty liver of obesity via upregulation of the pathways of lipid biosynthesis in the liver.
Comment in
-
Obstructive sleep apnea: wreaking havoc with homeostasis.J Appl Physiol (1985). 2005 Nov;99(5):1634-5. doi: 10.1152/japplphysiol.00858.2005. J Appl Physiol (1985). 2005. PMID: 16227456 No abstract available.
Similar articles
-
Methionine restriction prevents the progression of hepatic steatosis in leptin-deficient obese mice.Metabolism. 2013 Nov;62(11):1651-61. doi: 10.1016/j.metabol.2013.06.012. Epub 2013 Aug 5. Metabolism. 2013. PMID: 23928105
-
Obstructive sleep apnea and dyslipidemia: implications for atherosclerosis.Curr Opin Endocrinol Diabetes Obes. 2010 Apr;17(2):161-5. doi: 10.1097/MED.0b013e3283373624. Curr Opin Endocrinol Diabetes Obes. 2010. PMID: 20125003 Free PMC article. Review.
-
Effect of deficiency in SREBP cleavage-activating protein on lipid metabolism during intermittent hypoxia.Physiol Genomics. 2007 Oct 22;31(2):273-80. doi: 10.1152/physiolgenomics.00082.2007. Epub 2007 Jul 31. Physiol Genomics. 2007. PMID: 17666524
-
Obstructive sleep apnea and chronic intermittent hypoxia: a review.Chin J Physiol. 2006 Oct 31;49(5):234-43. Chin J Physiol. 2006. PMID: 17294831 Review.
-
Intermittent hypoxia induces hyperlipidemia in lean mice.Circ Res. 2005 Sep 30;97(7):698-706. doi: 10.1161/01.RES.0000183879.60089.a9. Epub 2005 Aug 25. Circ Res. 2005. PMID: 16123334
Cited by
-
Potential Therapeutic Targets in Obesity, Sleep Apnea, Diabetes, and Fatty Liver Disease.J Clin Med. 2024 Apr 12;13(8):2231. doi: 10.3390/jcm13082231. J Clin Med. 2024. PMID: 38673503 Free PMC article. Review.
-
T266M variants of ANGPTL4 improve lipid metabolism by modifying their binding affinity to acetyl-CoA carboxylase in obstructive sleep apnea.Ann Med. 2024 Dec;56(1):2337740. doi: 10.1080/07853890.2024.2337740. Epub 2024 Apr 4. Ann Med. 2024. PMID: 38574398 Free PMC article.
-
A nationwide study on sleep complaints and associated factors in older adults: ELSI-Brazil.Cad Saude Publica. 2023 Nov 10;39(10):e00061923. doi: 10.1590/0102-311XEN061923. eCollection 2023. Cad Saude Publica. 2023. PMID: 38018640 Free PMC article.
-
Composite lipid indices in patients with obstructive sleep apnea: a systematic review and meta-analysis.Lipids Health Dis. 2023 Jun 29;22(1):84. doi: 10.1186/s12944-023-01859-3. Lipids Health Dis. 2023. PMID: 37386562 Free PMC article.
-
Association between sleep problems and multimorbidity patterns in older adults.BMC Public Health. 2023 May 26;23(1):978. doi: 10.1186/s12889-023-15965-5. BMC Public Health. 2023. PMID: 37237275 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous