Mechanisms of obesity and related pathology: linking immune responses to metabolic stress.
There is a tightly regulated interaction, which is well-conserved in evolution, between the metabolic and immune systems that is deranged in states of over- or under-nutrition. Obesity, an energy-rich condition, is characterized by the activation of an inflammatory process in metabolically active sites such as adipose tissue, liver and immune cells. The consequence of this response is a sharp increase in circulating levels of proinflammatory cytokines, adipokines and other inflammatory markers. Activation of the immune response in obesity is mediated by specific signaling pathways, with Jun N-terminal kinase and IkappaB kinase beta/nuclear factor kappa-light-chain-enhancer of activated B cells being the most well studied. It is known that the above events modify insulin signaling and result in the development of insulin resistance. The nutrient overload characterizing obesity is a metabolic stressor associated with intracellular organelle (e.g. the endoplasmic reticulum) stress. The exact characterization of the series of events and the mechanisms that integrate the inflammatory response with metabolic homeostasis at the cellular and systemic level is a very active research field. In this minireview, we discuss the signaling pathways and molecules associated with the development of obesity-induced inflammation, as well as the evidence that supports a critical role for the stress response in this process.
Karalis
Katia P
KP
Biomedical Research Foundation of the Academy of Athens (BRFAA), Greece. kkarali@bioacademy.gr
Giannogonas
Panagiotis
P
Kodela
Elisavet
E
Koutmani
Yassemi
Y
Zoumakis
Manolis
M
Teli
Thalia
T
D000818:Animals; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D009765:Obesity / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000276:immunology / Q000528:radiation effects; D015398:Signal Transduction
D051550:I-kappa B Kinase; D048031:JNK Mitogen-Activated Protein Kinases