Cadmium reduces adipocyte size and expression levels of adiponectin and Peg1/Mest in adipose tissue.
Adipose tissue dysfunction has been associated with diabetogenic effects. The effects of repeated Cd exposure on adipocytes remain largely unknown. We administered Cd at doses of 0, 5, 10, and 20 micromol/kgbw sc for 2 weeks (3.5 times/week) to mice and assessed the possible alteration of epididymal white adipose tissue (WAT), including histological difference, adipocyte differentiation and functional capacity. Whereas hepatic weight did not differ between the control and Cd-exposed groups, WAT weight, as well as adipose cell mass, significantly decreased in a dose-dependent manner in Cd-treated mice. The Cd concentration in WAT significantly increased in Cd-treated groups after 2 weeks of exposure. Next, we examined the effects of Cd on adipocyte differentiation and hypertrophy. Cd exposure significantly decreased the paternally expressed gene 1/Mesoderm-specific transcript mRNA expression levels. Both peroxisome proliferator-activated receptor gamma2 and CCAAT/enhancer-binding protein alpha mRNA expression levels in WAT tended to decrease in the Cd-treated groups. Next, we determined the effects of Cd exposure on the mRNA expression levels of adipose-derived hormones, such as adiponectin and resistin. The adiponectin mRNA expression level in WAT decreased after both 6h and 2 weeks of exposure to a high dose of Cd, and the reduction in resistin mRNA expression levels was observed after 2 weeks of exposure. These results suggest that Cd exposure causes abnormal adipocyte differentiation, expansion, and function, which might lead to development of insulin resistance, hypertension, and cardiovascular disease.
Kawakami
Takashige
T
Faculty of Pharmaceutical Science, Tokushima Bunri University, 180 Yamashiro-cho, Tokushima City 770-8514, Japan.
Sugimoto
Hiroyuki
H
Furuichi
Rie
R
Kadota
Yoshito
Y
Inoue
Masahisa
M
Setsu
Kojun
K
Suzuki
Shinya
S
Sato
Masao
M
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D004435:Eating / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008668:Metallothionein / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects
D052242:Adiponectin; D047495:PPAR gamma; D011506:Proteins; D012333:RNA, Messenger; C103637:mesoderm specific transcript protein; D002104:Cadmium; D008668:Metallothionein