Cited by 319Adipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and MetabolismPeroxisome Proliferator-Activated Receptors

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Role of hypoxia in obesity-induced disorders of glucose and lipid metabolism in adipose tissue.

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Yin, Jun, Gao, Zhanguo, He, Qing, Zhou, Dequan, Guo, ZengKui, Ye, Jianping·2009·American Journal of Physiology-Endocrinology and Metabolism

DOI 10.1152/ajpendo.90760.2008PMC PMC2645021

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Abstract

Recent studies suggest that adipose tissue hypoxia (ATH) may contribute to endocrine dysfunction in adipose tissue of obese mice. In this study, we examined hypoxia's effects on metabolism in adipocytes. We determined the dynamic relationship of ATH and adiposity in ob/ob mice. The interstitial oxygen pressure (Po(2)) was monitored in the epididymal fat pads for ATH. During weight gain from 39.5 to 55.5 g, Po(2) declined from 34.8 to 20.1 mmHg, which are 40-60% lower than those in the lean mice. Insulin receptor-beta (IRbeta) and insulin receptor substrate-1 (IRS-1) were decreased in the adipose tissue of obese mice, and the alteration was observed in 3T3-L1 adipocytes after hypoxia (1% oxygen) treatment. Insulin-induced glucose uptake and Akt Ser(473) phosphorylation was blocked by hypoxia in the adipocytes. This effect of hypoxia exhibited cell type specificity, as it was not observed in L6 myotubes and betaTC6 cells. In response to hypoxia, free fatty acid (FFA) uptake was reduced and lipolysis was increased in 3T3-L1 adipocytes. The molecular mechanism of decreased fatty acid uptake may be related to inhibition of fatty acid transporters (FATP1 and CD36) and transcription factors (PPARgamma and C/EBPalpha) by hypoxia. The hypoxia-induced lipolysis was observed in vivo after femoral arterial clamp. Necrosis and apoptosis were induced by hypoxia in 3T3-L1 adipocytes. These data suggest that ATH may promote FFA release and inhibit glucose uptake in adipocytes by inhibition of the insulin-signaling pathway and induction of cell death.

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Additional file 7 of Using RNA-seq to identify suitable housekeeping genes for hypoxia studies in human adipose-derived stem cells
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Additional file 10 of Multi-omics analysis reveals the glycolipid metabolism response mechanism in the liver of genetically improved farmed Tilapia (GIFT, Oreochromis niloticus) under hypoxia stress
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Additional file 5 of Using RNA-seq to identify suitable housekeeping genes for hypoxia studies in human adipose-derived stem cells
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Additional file 2 of Multi-omics analysis reveals the glycolipid metabolism response mechanism in the liver of genetically improved farmed Tilapia (GIFT, Oreochromis niloticus) under hypoxia stress
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Additional file 11 of Multi-omics analysis reveals the glycolipid metabolism response mechanism in the liver of genetically improved farmed Tilapia (GIFT, Oreochromis niloticus) under hypoxia stress
Ma, J., Qiang, J., Tao, Y.-F., Bao, J.-W., Zhu, H.-J., Li, L.-G., & Xu, P. (2021) · Figshare · doi:10.6084/m9.figshare.13727606
Additional file 1 of Multi-omics analysis reveals the glycolipid metabolism response mechanism in the liver of genetically improved farmed Tilapia (GIFT, Oreochromis niloticus) under hypoxia stress
Ma, J., Qiang, J., Tao, Y., Bao, J.-W., Zhu, H.-J., Li, L.-G., & Xu, P. (2021) · Figshare · doi:10.6084/m9.figshare.13727609
Additional file 5 of Multi-omics analysis reveals the glycolipid metabolism response mechanism in the liver of genetically improved farmed Tilapia (GIFT, Oreochromis niloticus) under hypoxia stress
Ma, J., Qiang, J., Tao, Y., Bao, J.-W., Zhu, H.-J., Li, L.-G., & Xu, P. (2021) · Figshare · doi:10.6084/m9.figshare.13727621
Additional file 4 of Using RNA-seq to identify suitable housekeeping genes for hypoxia studies in human adipose-derived stem cells
Ong, H. T., Prêle, C. M., & Rodney, D. (2024) · Figshare · doi:10.6084/m9.figshare.26582648

Authors: Yin, J., Gao, Z., He, Q., Zhou, D., Guo, Z., & Ye, J.
Affiliations: Pennington Biomedical Research Center (US)
ORCID: Yin, Jun
He, Qing
Zhou, Dequan
Ye, Jianping
Venue: American Journal of Physiology-Endocrinology and Metabolism
Publisher: American Physiological Society
Published: 2009-02
Volume: 296
Issue: 2
Pages: E333-E342
ISSN: 0193-1849 (ISSN-L)
1522-1555
DOI: 10.1152/ajpendo.90760.2008
PMC: PMC2645021
OpenAlex: W2150350398
Cited by: 319
References: 59
Citations by year: 2026: 7 · 2025: 6 · 2024: 25 · 2023: 13 · 2022: 19 · 2021: 26 · 2020: 21 · 2019: 15 · 2018: 15 · 2017: 28 · 2016: 10 · 2015: 17 · 2014: 19 · 2013: 31 · 2012: 24
FWCI: 10.64
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: American Diabetes Association
National Institute of Diabetes and Digestive and Kidney Diseases (R56DK068036, R01DK068036, DK 68036, P30DK072476)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
Keywords: adipose tissue hypoxia, obesity, insulin signaling, insulin receptor beta, IRS-1, Akt phosphorylation, glucose uptake, fatty acid uptake, lipolysis, free fatty acid release, adipocyte apoptosis, adipocyte necrosis, PPARγ, C/EBPα, FATP1, CD36, ob/ob mice
MeSH terms: Adipose Tissue, Animals, Cells, Cultured, Diet, Atherogenic, Gene Expression Regulation, Glucose, Insulin, Male, Mice, Inbred C57BL, Mice, Obese, Obesity, Cell Hypoxia, 3T3-L1 Cells, Glucose Metabolism Disorders, Mice, Rats, Lipid Metabolism Disorders

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Role of hypoxia in obesity-induced disorders of glucose and lipid metabolism in adipose tissue.

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