Inflamed adipose tissue: a culprit underlying the metabolic syndrome and atherosclerosis.
The metabolic syndrome is associated with a dysregulated adipose tissue; in part a consequence of adipose cell enlargement and the associated infiltration of macrophages. Adipose cell enlargement leads to a proinflammatory state in the cells with reduced secretion of adiponectin and with increased secretion of several cytokines and chemokines including interleukin (IL)-6, IL-8, and MCP-1. MCP-1 has been shown to play an important role for the associated recruitment of macrophages into the adipose tissue. The increased release of cytokines leads to an impaired differentiation of the preadipocytes with reduced lipid accumulation and induction of adiponectin, thus promoting ectopic lipid storage. In particular tumor necrosis factor (TNF) alpha, but also IL-6, has been shown to induce these effects in preadipocytes and this is associated with an increased Wnt signaling maintaining the cells in an undifferentiated and proinflammatory state. The proinflammatory state in the adipose tissue also leads to a local insulin resistance including an impaired inhibitory effect of insulin on FFA release. The insulin resistance further supports the proinflammatory state because insulin, by itself, is both antilipolytic and antiinflammatory by antagonizing cytokine-induced activation of STAT signaling.
Gustafson
Birgit
B
The Lundberg Laboratory for Diabetes Research, Center of Excellence for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden.
Hammarstedt
Ann
A
Andersson
Christian X
CX
Smith
Ulf
U
D050156:Adipogenesis / Q000276:immunology; D000273:Adipose Tissue / Q000276:immunology*; D050197:Atherosclerosis / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D007328:Insulin / Q000502:physiology; D008262:Macrophage Activation / Q000276:immunology; D024821:Metabolic Syndrome / Q000276:immunology* / Q000503:physiopathology