Adipose Tissue Hypoxia and Inflammation in Obesity Abstract: Recent studies from several labs including ours consistently support that adipose tissue hypoxia (ATH) may be responsible for the initiation of chronic inflammation and adipose tissue dysfunction in obese subjects. The observations have been reported in both human and mice. The biological significance of ATH has been highlighted in several review articles about inflammation and adipose tissue function in obesity. However, the uptream and downstream events of ATH remains unknown in vivo. Based on our data, we hypothesize that the chronic inflammation represents a major event of hypoxia response in the adipose tissue in obesity. To test this hypothesis, we would propose three specific aims.
AIM I. To test that adipose tissue hypoxia is a result of blood flow reduction. Blood flow and oxygen tension will be examined in adipose tissue to test the relationship in vivo. Diet-induced obese mice and ob/ob mice will be used.
AIM II. To determine that the blood flow reduction is a consequence of microcirculation failure in the adipose tissue. The microcirculation will be investigated by analyzing vascular structure and function. The study will focus on angiogenesis, and vasodilation. Angiogenic factors and vessel tone regulators will be analyzed during adipose tissue growth.
AIM III. To test that inflammation mediates the hypoxia signal in the regulation of adipose tissue vasculature. A role of macrophage in angiogenesis will be investigated in adipocyte-specific NF-kB p65 knockout mice. We expect that in the absence of NF-kB p65, macrophage function will be decreased in adipose tissue and angiogenesis will be defective. We expect that this study will provide a novel mechanism for chronic inflammation and adipose tissue dysfunction in obesity. Adipose tissue hypoxia has potential to be a new biomarker for early diagnosis of insulin resistance.

Public Health Relevance

Inflammation in obesity contributes to many chronic diseases in obese patients. Understanding of the mechanism of inflammation will help us to develop strategies in prevention and treatment of the chronic diseases, such as type 2 diabetes, hypertension, heart attack, atherosclerosis, hyperglycemia, renal failure and blindness. However, the current knowledge is not sufficient to provide a clear molecular target in preventive or therapeutic intervention of these diseases. In this study, we plan to identify the earlier biomarkers for diagnosis of the inflammation and insulin resistance in obese condition.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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Integrative Physiology of Obesity and Diabetes Study Section (IPOD)
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Haft, Carol R
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Lsu Pennington Biomedical Research Center
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Baton Rouge
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Lee, J H; Zhang, Y; Zhao, Z et al. (2017) Intracellular ATP in balance of pro- and anti-inflammatory cytokines in adipose tissue with and without tissue expansion. Int J Obes (Lond) 41:645-651
Hao, Zheng; Mumphrey, Michael B; Townsend, R Leigh et al. (2016) Reprogramming of defended body weight after Roux-En-Y gastric bypass surgery in diet-induced obese mice. Obesity (Silver Spring) 24:654-60
Sun, Jingquan; Ye, Xin; Xie, Minhao et al. (2016) Induction of triglyceride accumulation and mitochondrial maintenance in muscle cells by lactate. Sci Rep 6:33732
Hao, Z; Mumphrey, M B; Morrison, C D et al. (2016) Does gastric bypass surgery change body weight set point? Int J Obes Suppl 6:S37-S43
Lu, H; Gao, Z; Zhao, Z et al. (2016) Transient hypoxia reprograms differentiating adipocytes for enhanced insulin sensitivity and triglyceride accumulation. Int J Obes (Lond) 40:121-8
Karkeni, Esma; Astier, Julien; Tourniaire, Franck et al. (2016) Obesity-associated Inflammation Induces microRNA-155 Expression in Adipocytes and Adipose Tissue: Outcome on Adipocyte Function. J Clin Endocrinol Metab 101:1615-26
Xu, Fen; Zheng, Xiaobin; Lin, Beisi et al. (2016) Diet-induced obesity and insulin resistance are associated with brown fat degeneration in SIRT1-deficient mice. Obesity (Silver Spring) 24:634-42
Zhang, Yong; Zhao, Zhiyun; Ke, Bilun et al. (2016) Induction of Posttranslational Modifications of Mitochondrial Proteins by ATP Contributes to Negative Regulation of Mitochondrial Function. PLoS One 11:e0150454
Hao, Z; M├╝nzberg, H; Rezai-Zadeh, K et al. (2015) Leptin deficient ob/ob mice and diet-induced obese mice responded differently to Roux-en-Y bypass surgery. Int J Obes (Lond) 39:798-805
Goldsmith, Felicia; Keenan, Michael J; Raggio, Anne M et al. (2015) Induction of Energy Expenditure by Sitagliptin Is Dependent on GLP-1 Receptor. PLoS One 10:e0126177

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