Meeting abstract | Open | Published:
Hypoxia in obesity - from bench to bedside
Journal of Translational Medicinevolume 10, Article number: A20 (2012)
It is generally accepted that hypoxia is related to sleep apnea in obesity. This concept has been changed since the report of hypoxia response in adipose tissue of obese mice by our group in 2007 . The observation has been confirmed by many laboratories in multiple obesity model systems including mouse and human [2–8]. The adipose tissue hypoxia has been a new concept to explain the adipose tissue dysfunction in obesity [9, 10]. It provides a unified answer to all of the pathological changes in the adipose tissue under obesity, such as chronic inflammation, ER stress, leptin expression, adiponectin reduction, adipocyte death, elevated lipolysis and adipocyte insulin resistance [9, 10]. Studies suggest that capillary dysfunction occurs during expansion of adipose tissue [11, 12], and leads to reduction in adipose blood supply , which is responsible for the tissue hypoxia. In this aspect, the adipose tissue dysfunction is a result of local vascular failure in obesity . In addition, the hypoxia-induced inflammation response has beneficial effects in the body. For example, inflammatory response stimulates adipose tissue remodeling [11, 14] and promotes energy expenditure to fight against obesity [15, 16]. These new insights into the adipose tissue biology suggest that the hypoxia response may be a feedback mechanism in the protection of body against obesity. In translation of this view into clinical setting, it is believed that sleep apnea is also a protection mechanism in the body to maintain energy homeostasis in obesity. It uses the hypoxia response to trigger the onset of multiple protection mechanisms in the body.
Ye J, Gao Z, Yin J, He H: Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice. Am J Physiol Endocrinol Metab. 2007, 293: E1118-E1128. 10.1152/ajpendo.00435.2007.
Hosogai N, Fukuhara A, Oshima K, Miyata Y, Tanaka S, Segawa K, Furukawa S, Tochino Y, Komuro R, Matsuda M: Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation. Diabetes. 2007, 56 (4): 901-911. 10.2337/db06-0911.
Greenstein AS, Khavandi K, Withers SB, Sonoyama K, Clancy O, Jeziorska M, Laing I, Yates AP, Pemberton PW, Malik RA: Local inflammation and hypoxia abolish the protective anticontractile properties of perivascular fat in obese patients. Circulation. 2009, 119 (12): 1661-1670. 10.1161/CIRCULATIONAHA.108.821181.
Yin J, Gao Z, He Q, Ye J: Role of hypoxia in obesity-induced disorders of glucose and lipid metabolism in adipose tissue. Am J Physiol Endocrinol Metab. 2009, 296: E333-E342.
Rausch ME, Weisberg S, Vardhana P, Tortoriello DV: Obesity in C57BL/6J mice is characterized by adipose tissue hypoxia and cytotoxic T-cell infiltration. Int J Obes (Lond). 2008, 32 (3): 451-463. 10.1038/sj.ijo.0803744.
Pasarica M, Sereda OR, Redman LM, Albarado DC, Hymel DT, Roan LE, Rood JC, Burk DH, Smith SR: Reduced adipose tissue oxygenation in human obesity: evidence for rarefaction, macrophage chemotaxis, and inflammation without an angiogenic response. Diabetes. 2009, 58 (3): 718-725.
Pasarica M, Rood J, Ravussin E, Schwarz JM, Smith SR, Redman LM: Reduced oxygenation in human obese adipose tissue is associated with impaired insulin suppression of lipolysis. The Journal of clinical endocrinology and metabolism. 2010, 95 (8): 4052-4055. 10.1210/jc.2009-2377.
Zhang L, Ebenezer PJ, Dasuri K, Fernandez-Kim SO, Francis J, Mariappan N, Gao Z, Ye J, Bruce-Keller A, Keller JN: Aging is associated with hypoxia and oxidative stress in adipose tissue: Implications for adipose function. American journal of physiology-Endocrinology and metabolism. 2011, 301 (4): E599-E607. 10.1152/ajpendo.00059.2011.
Ye J: Emerging Role of Adipose Tissue Hypoxia in Obesity and Insulin Resistance. Int J Obes. 2009, 33 (1): 54-66. 10.1038/ijo.2008.229.
Trayhurn P, Wang B, Wood IS: Hypoxia in adipose tissue: a basis for the dysregulation of tissue function in obesity?. Br J Nutr. 2008, 1-9.
Pang C, Gao Z, Yin J, Zhang J, Jia W, Ye J: Macrophage Infiltration into Adipose Tissue May Promote Angiogenesis for Adipose Tissue Remodeling in Obesity. Am J Physiol Endocrinol Metab. 2008, 295: E313-E322. 10.1152/ajpendo.90296.2008.
Gealekman O, Guseva N, Hartigan C, Apotheker S, Gorgoglione M, Gurav K, Tran KV, Straubhaar J, Nicoloro S, Czech MP: Depot-Specific Differences and Insufficient Subcutaneous Adipose Tissue Angiogenesis in Human Obesity. Circulation. 2011, 123 (2): 186-194. 10.1161/CIRCULATIONAHA.110.970145.
Ye J: Adipose Tissue Vascularization: Its Role in Chronic Inflammation. Current diabetes reports. 2011, 11 (3): 203-210. 10.1007/s11892-011-0183-1.
Halberg N, Khan T, Trujillo ME, Wernstedt-Asterholm I, Attie AD, Sherwani S, Wang ZV, Landskroner-Eiger S, Dineen S, Magalang UJ: HIF 1 alpha Induces Fibrosis and Insulin Resistance in White Adipose Tissue. Mol Cell Biol. 2009, 29 (16): 4467-4483. 10.1128/MCB.00192-09.
Tang T, Zhang J, Yin J, Staszkiewicz J, Gawronska-Kozak B, Mynatt R, Martin RJ, Keenan M, Gao Z, Ye J: Uncoupling of Inflammation and Insulin Resistance by NF-kB in Transgenic Mice through Induction of Energy Expenditure. J Biol Chem. 2010, 285: 4637-4644. 10.1074/jbc.M109.068007.
Jiao P, Feng B, Ma J, Nie Y, Paul E, Li Y, Xu H: Constitutive Activation of IKKβ in Adipose Tissue Prevents Diet-Induced Obesity in Mice. Endocrinology. 2012, 153 (1): 154-165. 10.1210/en.2011-1346.