Alterations of the classic pathway of complement in adipose tissue of obesity and insulin resistance.
Adipose tissue inflammation has recently been linked to the pathogenesis of obesity and insulin resistance. C1 complex comprising three distinct proteins, C1q, C1r, and C1s, involves the key initial activation of the classic pathway of complement and plays an important role in the initiation of inflammatory process. In this study, we investigated adipose expression and regulation of C1 complement subcomponents and C1 activation regulator decorin in obesity and insulin resistance. Expression of C1q in epididymal adipose tissue was increased consistently in ob/ob mice, Zucker obese rats, and high fat-diet-induced obese (HF-DIO) mice. Decorin was found to increase in expression in Zucker obese rats and HF-DIO mice but decrease in ob/ob mice. After TZD administration, C1q and decorin expression was reversed in Zucker obese rats and HF-DIO mice. Increased expression of C1 complement and decorin was observed in both primary adipose and stromal vascular cells isolated from Zucker obese rats. Upregulation of C1r and C1s expression was also perceived in adipose cells from insulin-resistant humans. Furthermore, expression of C1 complement and decorin is dysregulated in TNF-alpha-induced insulin resistance in 3T3-L1 adipocytes and cultured rat adipose cells as they become insulin resistant after 24-h culture. These data suggests that both adipose and immune cells are the sources for abnormal adipose tissue production of C1 complement and decorin in obesity. Our findings also demonstrate that excessive activation of the classic pathway of complement commonly occurs in obesity, suggesting its possible role in adipose tissue inflammation and insulin resistance.
Zhang
Jinhui
J
Department of Food Science and Nutrition, University of Minnesota, St. Paul, Minnesota 55108-1038, USA.
Wright
Wendy
W
Bernlohr
David A
DA
Cushman
Samuel W
SW
Chen
Xiaoli
X
D041721:3T3-L1 Cells; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D002839:Chromans / Q000494:pharmacology; D015922:Complement C1q / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D015923:Complement C1r / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D003173:Complement C1s / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D003171:Complement Pathway, Classical / Q000187:drug effects / Q000502:physiology*; D058575:Decorin; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker; D020133:Reverse Transcriptase Polymerase Chain Reaction; D045162:Thiazolidinediones / Q000494:pharmacology; D000077288:Troglitazone
D002839:Chromans; C546878:DCN protein, human; C546879:Dcn protein, mouse; C546880:Dcn protein, rat; D058575:Decorin; D016326:Extracellular Matrix Proteins; D007004:Hypoglycemic Agents; D011509:Proteoglycans; D012333:RNA, Messenger; D045162:Thiazolidinediones; D015922:Complement C1q; D015923:Complement C1r; D003173:Complement C1s; D000077288:Troglitazone