Expression and significance of lipin1 and AMPKα in hepatic insulin resistance in diet-induced insulin resistance rats.
BACKGROUND
Lipin1, a lately indentified adipokine, may link obesity with insulin resistance and diabetes. The present study aimed to investigate the changes and significance of lipin1 expression and lipin1-AMPK signaling in diet-induced hepatic insulin resistance.


METHODS
24 4-week-old Male Wistar rats were randomly divided into 2 groups: (1) control group (CO), (2) high-fat diet group (HF). Insulin sensitivity was evaluated by hyperinsulinemic-euglycemic clamp technique. The mRNA levels of α1 and α2 subunit of AMPKα as well as Lipin1 were measured using Real-time RT-PCR. The activities of AMPKα and Akt were evaluated by detection of p-AMPKα (Thr-172) and p-Akt (ser473) by Western blot.


RESULTS
After treatment of 4 months, HF group showed significantly increased levels of body weight, fasting plasma glucose and insulin levels; Plasma and liver total cholesterol (TC), triglycerides (TG) levels were also markedly elevated; Lipin1 expression at both mRNA and protein levels were significantly deceased. Compared with CO group, the mRNA and protein levels of AMPKα1 and AMPKα2 were not changed, whereas the p-AMPK (Thr-172) and p-AKT (ser473) levels in liver were significantly decreased in HF group.


CONCLUSIONS
These findings indicated that the decrease in lipin1 expression and AMPKα activation may contribute to hepatic insulin resistance in diet-induced obese rats.
Department of Endocrinology, The Second Hospital of Shandong University, 247 BeiYuan Road, JiNan, ShanDong, China.
S H
SH
Chen
X H
XH
Zhuang
Y T
YT
Liu
A L
AL
Sun
C R
CR
Chen
D055372:AMP-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D000818:Animals; D004032:Diet; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D007333:Insulin Resistance / Q000235:genetics*; D050356:Lipid Metabolism / Q000235:genetics; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D009765:Obesity / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D008055:Lipids; C530902:Lpin1 protein, rat; D009687:Nuclear Proteins; D055372:AMP-Activated Protein Kinases; C568305:Prkaa1 protein, rat