Inflammatory mediators and insulin resistance in obesity: role of nuclear receptor signaling in macrophages.
Visceral obesity is coupled to a general low-grade chronic inflammatory state characterized by macrophage activation and inflammatory cytokine production, leading to insulin resistance (IR). The balance between proinflammatory M1 and antiinflammatory M2 macrophage phenotypes within visceral adipose tissue appears to be crucially involved in the development of obesity-associated IR and consequent metabolic abnormalities. The ligand-dependent transcription factors peroxisome proliferator activated receptors (PPARs) have recently been implicated in the determination of the M1/M2 phenotype. Liver X receptors (LXRs), which form another subgroup of the nuclear receptor superfamily, are also important regulators of proinflammatory cytokine production in macrophages. Disregulation of macrophage-mediated inflammation by PPARs and LXRs therefore underlies the development of IR. This review summarizes the role of PPAR and LXR signaling in macrophages and current knowledge about the impact of these actions in the manifestation of IR and obesity comorbidities such as liver steatosis and diabetic osteopenia.
Department of Regenerative Cardiology, Centro Nacional de Investigaciones Cardiovasculares, Instituto de Salud Carlos III, 28029 Madrid, Spain.
Lucía
L
Fuentes
Tamás
T
Roszer
Mercedes
M
Ricote
D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D000818:Animals; D001862:Bone Resorption / Q000209:etiology; D005234:Fatty Liver / Q000209:etiology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D000071518:Liver X Receptors; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D009765:Obesity / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D057093:Orphan Nuclear Receptors / Q000378:metabolism*; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D018836:Inflammation Mediators; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D047492:Peroxisome Proliferator-Activated Receptors