title: Adipose tissue inflammation and ectopic lipid accumulation.
abstract: Obesity may be viewed as a chronic low-grade inflammatory disease as well as a metabolic disease.  Indeed, unbalanced production of pro- and anti-inflammatory adipocytokines critically contributes to the obesity-induced insulin resistance.  In addition to lipid-laden mature adipocytes, adipose tissue is composed of various stromal cells such as preadipocytes, endothelial cells, fibroblasts, and immune cells that may be involved in adipose tissue functions.  Accumulating evidence has suggested that adipocytes and stromal cells in adipose tissue change dramatically in number and cell type during the course of obesity, which is referred to as "adipose tissue remodeling."  Among stromal cells, infiltration of macrophages in obese adipose tissue precedes the development of insulin resistance in animal models, suggesting that they are crucial for adipose tissue inflammation.  We have provided evidence suggesting that a paracrine loop involving saturated fatty acids and tumor necrosis factor-α derived from adipocytes and macrophages, respectively, aggravates obesity-induced adipose tissue inflammation.  On the other hand, storing excessive energy as triglyceride is also a fundamental function of adipose tissue.  Recent evidence suggests that reduced lipid storage in obese adipose tissue contributes to ectopic lipid accumulation in non-adipose tissues such as the liver, skeletal muscle, and pancreas, where lipotoxicity impairs their metabolic functions.  Notably, chronic inflammation is capable of inducing insulin resistance, lipolysis, and interstitial fibrosis in adipose tissue, all of which may reduce the lipid-storing function.  Understanding the molecular mechanism underlying adipose tissue remodeling may lead to the identification of novel therapeutic strategies to prevent or treat obesity-induced adipose tissue inflammation.
authors.affiliation: Department of Molecular Medicine and Metabolism, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Suganami
authors.forename: Miyako
authors.initials: M
authors.lastname: Tanaka
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ogawa
mesh_terms: D051700:Activating Transcription Factor 3 / Q000502:physiology; D017667:Adipocytes / Q000378:metabolism / Q000473:pathology; D054392:Adipokines / Q000502:physiology; D000273:Adipose Tissue / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D007333:Insulin Resistance / Q000502:physiology; D050356:Lipid Metabolism / Q000502:physiology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009765:Obesity / Q000473:pathology; D019899:Paracrine Communication / Q000502:physiology
chemical_list: C490449:ATF3 protein, human; D051700:Activating Transcription Factor 3; D054392:Adipokines; D002352:Carrier Proteins; D005227:Fatty Acids; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human