MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity.
Adipocytes secrete a variety of bioactive molecules that affect the insulin sensitivity of other tissues. We now show that the abundance of monocyte chemoattractant protein-1 (MCP-1) mRNA in adipose tissue and the plasma concentration of MCP-1 were increased both in genetically obese diabetic (db/db) mice and in WT mice with obesity induced by a high-fat diet. Mice engineered to express an MCP-1 transgene in adipose tissue under the control of the aP2 gene promoter exhibited insulin resistance, macrophage infiltration into adipose tissue, and increased hepatic triglyceride content. Furthermore, insulin resistance, hepatic steatosis, and macrophage accumulation in adipose tissue induced by a high-fat diet were reduced extensively in MCP-1 homozygous KO mice compared with WT animals. Finally, acute expression of a dominant-negative mutant of MCP-1 ameliorated insulin resistance in db/db mice and in WT mice fed a high-fat diet. These findings suggest that an increase in MCP-1 expression in adipose tissue contributes to the macrophage infiltration into this tissue, insulin resistance, and hepatic steatosis associated with obesity in mice.
Kanda
Hajime
H
Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Tateya
Sanshiro
S
Tamori
Yoshikazu
Y
Kotani
Ko
K
Hiasa
Ken-ichi
K
Kitazawa
Riko
R
Kitazawa
Sohei
S
Miyachi
Hitoshi
H
Maeda
Sakan
S
Egashira
Kensuke
K
Kasuga
Masato
M
D016475:3T3 Cells; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D018932:Chemokine CCL2 / Q000097:blood* / Q000235:genetics; D004041:Dietary Fats; D005234:Fatty Liver; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D008822:Mice, Transgenic; D009765:Obesity / Q000503:physiopathology*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D004041:Dietary Fats; D012333:RNA, Messenger; D014280:Triglycerides; D005947:Glucose