Hypoxia and Adipose Tissue Function and Dysfunction in Obesity

Abstract

The rise in the incidence of obesity has led to a major interest in the biology of white adipose tissue. The tissue is a major endocrine and signaling organ, with adipocytes, the characteristic cell type, secreting a multiplicity of protein factors, the adipokines. Increases in the secretion of a number of adipokines occur in obesity, underpinning inflammation in white adipose tissue and the development of obesity-associated diseases. There is substantial evidence, particularly from animal studies, that hypoxia develops in adipose tissue as the tissue mass expands, and the reduction in Po2is considered to underlie the inflammatory response. Exposure of white adipocytes to hypoxic conditions in culture induces changes in the expression of >1,000 genes. The secretion of a number of inflammation-related adipokines is upregulated by hypoxia, and there is a switch from oxidative metabolism to anaerobic glycolysis. Glucose utilization is increased in hypoxic adipocytes with corresponding increases in lactate production. Importantly, hypoxia induces insulin resistance in fat cells and leads to the development of adipose tissue fibrosis. Many of the responses of adipocytes to hypoxia are initiated at Po2levels above the normal physiological range for adipose tissue. The other cell types within the tissue also respond to hypoxia, with the differentiation of preadipocytes to adipocytes being inhibited and preadipocytes being transformed into leptin-secreting cells. Overall, hypoxia has pervasive effects on the function of adipocytes and appears to be a key factor in adipose tissue dysfunction in obesity.

PCR array and protein array studies demonstrate that IL-1β(interleukin-1β) stimulates the expression and secretion of multiple cytokines and chemokines in human adipocytes

“…White adipose tissue is a major endocrine and secretory organ, with white adipocytes releasing a multiplicity of factors in the form of diverse adipokines, as well as fatty acids and other lipid moieties (Frühbeck et al, 2001;Trayhurn & Beattie, 2001;Rajala et al, 2003;Trayhurn, 2013). A number of adipokines are associated with the immune system and inflammation, and the expression and secretion of some of these protein signals and factors rise in obesity (Rajala et al, 2003;Hotamisligil, 2006;Trayhurn, 2013); examples include TNFα (tumour necrosis factor α), IL-6 (interleukin-6) and leptin. A notable exception is the hormone adiponectin, with its anti-inflammatory and insulin sensitising actions (Ouchi et al, 1999;Yokota et al, 2000;Berg et al, 2001;Yamauchi et al, 2001), the production and secretion of which falls as fat mass expands (Arita et al, 1999;Hotta et al, 2000).…”

MECHANISMS IN ENDOCRINOLOGY: White, brown and pink adipocytes: the extraordinary plasticity of the adipose organ

“…White adipocytes secrete a number of adipokines that affect eating behaviour (leptin) (20) and metabolism (e.g. adiponectin, resistin, adipsin) (21). Brown adipocytes also secrete hormones and growth factors (e.g.…”

Hypoxia: a consequence of obesity and also a tool to treat excessive weight loss

“…Thus, one of the mechanisms triggering inflammation has been associated with adipose tissue hypoxia [4] or increased oxygen tension [5], which affect a number of genes such as HIF-1a, MCP-1, IL-6, GLUT-1, ANGPTL-4 and PPAR-γ [6] that could be involved as a cause or as a consequence reaction to pathologically low or high oxygen conditions. Interestingly, as we hypothesized previously [3] and Kong et al have nicely demonstrated in their article [1], hypoxia is not only an ethological factor or a manifestation of disease, but also a therapeutic tool following different patterns (hypoxic exposure, hypoxic training, intermittent hypoxia under hyperbaric and normobaric conditions), which has been used for pre-acclimation in climbers, or to improve athletes performance as well as for heart, respiratory and nervous system diseases or to regulate body weight [7].…”