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Hypoxia-inducible factors: new strategies for treatment of obesity-induced metabolic diseases
  1. Sung Sik Choe1,
  2. Jae Bum Kim2
  1. 1 Institute of Molecular Biology and Genetics, Seoul National University, Seoul, Korea (the Republic of)
  2. 2 Institute of Molecular Biology and Genetics, Department of Biological Sciences, Seoul National University, Seoul, Korea (the Republic of)
  1. Correspondence to Dr Jae Bum Kim, Institute of Molecular Biology & Genetics, Department of Biological Sciences, Seoul National University, Seoul 08826, Korea (the Republic of); jaebkim{at}

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Adipose tissue inflammation has been proposed as a critical link between obesity and metabolic diseases, such as type 2 diabetes and cardiovascular diseases. In obese adipose tissue, macrophages and other immune cells are accumulated, triggering chronic inflammation. Elevated proinflammatory immune cells not only dysregulate adipose tissue function but also subsequently elicit systemic inflammation through the production of inflammatory mediators. Particularly, inflammatory cytokines from adipose tissue have been implicated in the pathogenesis of metabolic disorder, including insulin resistance in peripheral tissues.1 As the correlation between adipose tissue inflammation and metabolic diseases has been well established, the resolution of adipose tissue inflammation using anti-inflammatory agents, including nonsteroidal anti-inflammatory drugs, has gained the attention as one of the therapeutic potentials for prevention and treatment of obesity-induced metabolic diseases.2 In addition, evidence of the relationship between inflammation and hypoxia in obese adipose tissue has highlighted hypoxia-inducible factors (HIFs) as a novel target against adipose tissue inflammation.

In obesity, pathological expansion of adipose tissue leads to local hypoxia through several factors, such as adipocyte enlargement, insufficient neovascularisation, decreased blood flow and increased uncoupling respiration.3 Adipose tissue hypoxia could stabilise and activate HIFs that are the key transcription factors to mediate hypoxic responses, such as angiogenesis, vasodilation, erythropoiesis and glycolysis. HIFs are heterodimers composed of oxygen-sensitive α subunit (HIF-α) and constitutively expressed β subunit (HIF-1β). Duplication of ancestral HIF-α coincided with the evolution of vertebrates, and three α subunits …

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  • Contributors SSC and JBK, the cocorresponding authors, wrote and revised the manuscript before submission.

  • Funding This research was supported by the National Creative Research Initiative Programme (2011–0018312) and Basic Science Research Programme (NRF-2018R1A6A3A11043137) through the National Research Foundation of Korea funded by the Ministry of Education.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; internally peer reviewed.