Chronic intermittent hypoxia upregulates genes of lipid biosynthesis in obese mice

Jianguo Li, Dmitry N. Grigoryev, Shui Qing Ye, Laura Thorne, Alan R Schwartz, Philip L Smith, Christopher P. O'Donnell, Vsevolod Polotsky

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1643-1648
Number of pages6
JournalJournal of Applied Physiology
Volume99
Issue number5
DOIs
StatePublished - Nov 2005

Fingerprint

Obese Mice
Up-Regulation
Lipids
Liver
Obstructive Sleep Apnea
Sterol Regulatory Element Binding Protein 1
Genes
Cholesterol
Fatty Liver
Gene Expression
Real-Time Polymerase Chain Reaction
Phospholipids
Triglycerides
Sterol Regulatory Element Binding Protein 2
Fatty Acids
Acetate-CoA Ligase
Obesity
Enzymes and Coenzymes
Acetyl-CoA Carboxylase
Acyltransferases

Keywords

  • Fatty liver
  • Gene expression
  • Mouse
  • Obstructive sleep apnea

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this

Chronic intermittent hypoxia upregulates genes of lipid biosynthesis in obese mice. / Li, Jianguo; Grigoryev, Dmitry N.; Ye, Shui Qing; Thorne, Laura; Schwartz, Alan R; Smith, Philip L; O'Donnell, Christopher P.; Polotsky, Vsevolod.

In: Journal of Applied Physiology, Vol. 99, No. 5, 11.2005, p. 1643-1648.

Research output: Contribution to journalArticle

Li, Jianguo ; Grigoryev, Dmitry N. ; Ye, Shui Qing ; Thorne, Laura ; Schwartz, Alan R ; Smith, Philip L ; O'Donnell, Christopher P. ; Polotsky, Vsevolod. / Chronic intermittent hypoxia upregulates genes of lipid biosynthesis in obese mice. In: Journal of Applied Physiology. 2005 ; Vol. 99, No. 5. pp. 1643-1648.
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AU - Smith, Philip L

AU - O'Donnell, Christopher P.

AU - Polotsky, Vsevolod

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