Hypoxia as a Double-Edged Sword to Combat Obesity and Comorbidities

• Published in: Cells (Basel, Switzerland) Vol. 11; no. 23; p. 3735
• Main Authors: Wang, Ruwen, Sun, Qin, Wu, Xianmin, Zhang, Yiyin, Xing, Xiaorui, Lin, Kaiqing, Feng, Yue, Wang, Mingqi, Wang, Yibing, Wang, Ru
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 23.11.2022; MDPI
• Subjects: Adipocytes; Adipose tissue; Adipose Tissue - metabolism; Angiogenesis; Body fat; Body weight; Cardiovascular diseases; Care and treatment; Chronic diseases; Comorbidity; Complications and side effects; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 2 - metabolism; Diagnosis; Growth factors; Homeostasis; Humans; Hyperoxia; Hyperoxia - complications; Hypoxia; Hypoxia - metabolism; hypoxic; Inflammation; Lipids; Metabolic pathways; Metabolic syndrome; Metabolism; Mitochondria; Obesity; Obesity - metabolism; Overweight; Physiology; PO2; Proteins; Review; Risk factors; Therapeutic targets; Tumor necrosis factor-TNF; Weight control; China; adipose tissue; PO2; O2; hypoxic; obesity
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells11233735

The global epidemic of obesity is tightly associated with numerous comorbidities, such as type II diabetes, cardiovascular diseases and the metabolic syndrome. Among the key features of obesity, some studies have suggested the abnormal expansion of adipose-tissue-induced local endogenous hypoxic, while other studies indicated endogenous hyperoxia as the opposite trend. Endogenous hypoxic aggravates dysfunction in adipose tissue and stimulates secretion of inflammatory molecules, which contribute to obesity. In contrast, hypoxic exposure combined with training effectively generate exogenous hypoxic to reduce body weight and downregulate metabolic risks. The (patho)physiological effects in adipose tissue are distinct from those of endogenous hypoxic. We critically assess the latest advances on the molecular mediators of endogenous hypoxic that regulate the dysfunction in adipose tissue. Subsequently we propose potential therapeutic targets in adipose tissues and the small molecules that may reverse the detrimental effect of local endogenous hypoxic. More importantly, we discuss alterations of metabolic pathways in adipose tissue and the metabolic benefits brought by hypoxic exercise. In terms of therapeutic intervention, numerous approaches have been developed to treat obesity, nevertheless durability and safety remain the major concern. Thus, a combination of the therapies that suppress endogenous hypoxic with exercise plans that augment exogenous hypoxic may accelerate the development of more effective and durable medications to treat obesity and comorbidities.