Antagonistic effects of thiazolidinediones and cytokines in lipotoxicity.
Ectopic lipid accumulation is promoted by obesity and an impaired ability to accumulate triglycerides in the subcutaneous depots. The adipose tissue is dysregulated in hypertrophic obesity, i.e., when the adipose cells have become enlarged. In some individuals, however, obesity is a consequence of a recruitment of new adipocytes, i.e., a hyperplastic obesity. This form of obesity is usually not associated with the metabolic complications and is termed "obese but metabolically normal". We here review recent findings showing that hypertrophic obesity is associated with an impaired differentiation of committed preadipocytes. This may be a primary (genetic?) event, thus leading to hypertrophic fat cells and the associated inflammation. However, it is also possible that the inflammation is a primary event allowing, in particular, TNFalpha to inhibit preadipocyte differentiation. TNFalpha, instead, promotes a partial transdifferentiation of the preadipocytes to assume a macrophage-like phenotype. PPARgamma activation promotes adipogenesis but can apparently not overcome the impaired preadipocyte differentiation seen in hypertrophic obesity.
Smith
Ulf
U
The Lundberg Laboratory for Diabetes Research, Center of Excellence for Metabolic and Cardiovascular Research, Department of Molecular and Clinical Medicine, The Sahlgrenska Academy at the University of Gothenburg, SE-413 45 Gothenburg, Sweden. ulf.smith@medic.gu.se
Hammarstedt
Ann
A
D017667:Adipocytes / Q000378:metabolism; D050156:Adipogenesis; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D051379:Mice; D009765:Obesity / Q000378:metabolism* / Q000473:pathology; D047495:PPAR gamma / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D047495:PPAR gamma; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha