Increased levels of acylation-stimulating protein in interleukin-6-deficient (IL-6(-/-)) mice.
IL-6-deficient (IL-6(-/-)) mice develop obesity at 6-7 months of age. To elucidate the mechanisms of this mature-onset obesity, global gene expression profiles of 3-month-old preobese IL-6(-/-) were compared with those of IL-6(+/+) mice using DNA arrays. Genes that were up-regulated in IL-6(-/-) mice included the factors transthyretin and properdin in white adipose tissue and adipsin in muscle. These factors have been shown to influence the formation of acylation-stimulating protein (ASP), a cleavage product of complement C3. ASP stimulates the synthesis of triacylglycerol in adipocytes, and ASP-deficient mice are resistant to diet-induced obesity. In line with the increases in transthyretin, properdin, and adipsin, ASP levels in serum were increased by 31-54% in IL-6(-/-) compared with IL-6(+/+) mice. Furthermore, IL-6 replacement treatment in IL-6(-/-) mice decreased ASP levels significantly by 25-60%. In conclusion, ASP levels are increased in preobese IL-6(-/-) mice. This increase may result in increased triacylglycerol formation and uptake in IL-6(-/-) adipocytes and thereby contribute to the development of obesity in IL-6(-/-) mice.
Wernstedt
I
I
Research Center for Endocrinology and Metabolism, Wallenberg Laboratory, Sahlgrenska Academy, Sahlgrenska University Hospital, SE-41345 Goteborg, Sweden.
Olsson
B
B
Jernås
M
M
Paglialunga
S
S
Carlsson
L M S
LM
Smith
U
U
Cianflone
K
K
Wallenius
K
K
Wallenius
V
V
D017667:Adipocytes / Q000473:pathology; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D003176:Complement C3 / Q000378:metabolism; D015926:Complement C3a / Q000032:analysis* / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D015850:Interleukin-6 / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D011228:Prealbumin / Q000235:genetics; D011414:Properdin / Q000235:genetics; D014280:Triglycerides / Q000096:biosynthesis
D003176:Complement C3; D005230:Fatty Acids, Nonesterified; D015850:Interleukin-6; D011228:Prealbumin; D014280:Triglycerides; C044541:complement C3a, des-Arg-(77)-; D011414:Properdin; D015926:Complement C3a