Characterization of Wistar-Kyoto rats showing hyperadiponectinemia.
OBJECTIVE
Wistar-Kyoto rats (HA-WKY) kept in the author's laboratory showed higher levels of serum adiponectin (approximately 4-fold) compared with Wistar-Kyoto/Izm rats (WKY/Izm), a WKY standard strain, at 6weeks old. In a preliminary study, HA-WKY but not WKY/Izm showed hyperinsulinemia and severe hypercholesterolemia when fed a high-fat diet. This study analyzed the differences between HA-WKY and WKY/Izm to investigate the causes of hyperadiponectinemia.


METHODS
Six-week-old male HA-WKY and WKY/Izm were used for an analysis of adiponectin-related factors.


RESULTS
The main intermediates in the adiponectin signaling pathway, AMP-activated protein kinase and peroxisome proliferator-activated receptor alpha, were activated at similar levels in liver and skeletal muscle between HA-WKY and WKY/Izm, although HA-WKY had not only higher adiponectin concentrations but also extremely high levels of high-molecular weight (HMW, polymer) adiponectin, which is the active form. The main difference between HA-WKY and WKY/Izm was the existence of adiponectin, mainly middle-molecular weight (MMW, hexamer) and HMW adiponectin multimers, in skeletal muscle extracts from WKY/Izm but not HA-WKY. Skeletal muscle in WKY/Izm expressed much higher amounts of T-cadherin, a receptor for MMW and HMW adiponectin multimers, than that in HA-WKY. In contrast, there was no significant difference in the expression level of adiponectin receptor 2 for trimer, MMW, and HMW adiponectin multimers.


CONCLUSIONS
The results suggested that the existence of adiponectin in WKY/Izm skeletal muscle was due to the binding of serum adiponectin. The difference in serum adiponectin concentrations between HA-WKY and WKY/Izm could come from the difference in adiponectin binding to skeletal muscle.
Inoue
Takao
T
Department of Pathology, Kinki University School of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511 Japan.
Takemori
Kumiko
K
Yamamoto
Kazuo
K
Ito
Hiroyuki
H
D052242:Adiponectin / Q000097:blood* / Q000235:genetics*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D050356:Lipid Metabolism / Q000502:physiology; D008297:Male; D051381:Rats; D011921:Rats, Inbred WKY; D013045:Species Specificity
D052242:Adiponectin; D015415:Biomarkers