Cellular hypoxia: a key modulator of adipocyte function in obesity?
- Trayhurn, Paul
- Pérez de Heredia, Fátima
- Wang, Bohan
- Oliveira, Cristiane
- González-Muniesa, Pedro
- Wood, I. Stuart
ISSN: 1313-3705, 1313-3705
Año de publicación: 2009
Volumen: 1
Páginas: 19-26
Tipo: Artículo
Otras publicaciones en: Adipobiology
Objetivos de desarrollo sostenible
Resumen
We have proposed that hypoxia develops in adipose tissue (white) as tissue mass expands in obesity, this leading to the inflammatory response which is considered to underpin the development of obesity-associated diseases. Direct evidence for hypoxia in adipose tissue in obesity has now been obtained in mice and in humans. Studies on adipocytes, both human and murine, in cell culture have shown that the expression and release of several inflammation-related adipokines, such as IL-6, leptin and VEGF are stimulated by low pO2. The production of adiponectin, which has anti-inflammatory and insulin-sensitising actions, is, however, inhibited. Glucose uptake and the release of lactate are increased in adipocytes by hypoxia, with a corresponding increase in the level of the GLUT1 and MCT1 transporters, consistent with a switch to glycolytic metabolism. In preadipocytes, which do not normally synthesize leptin, low pO2 leads to induction of the expression and secretion of this key hormone. Recent studies suggest that there are important interactions between hypoxia and specific long-chain fatty acids in the production of inflammation-related adipokines. It is suggested that hypoxia has a pervasive effect on adipocyte physiology and is central to the dysregulation of adipose tissue function that occurs in obesity.