Impaired adiponectin-AMPK signalling in insulin-sensitive tissues of hypertensive rats.
OBJECTIVE
Adiponectin improves insulin sensitivity by decreasing lipid accumulation in insulin-sensitive tissues. The aim of this study was to investigate whether these effects are altered in hypertension.


METHODS
Adiponectin receptors (AdipoR1 and AdipoR2) and adiponectin-related enzymes were measured by real-time PCR and Western-blot in insulin-sensitive tissues of 10-week-old male spontaneously hypertensive rats (SHR). Intrahepatic and intramyocellular triglycerides were determined by enzymatic methods.


RESULTS
SHR showed overweight, dyslipidemia, glucose intolerance and insulin resistance. Circulating concentrations of adiponectin as well as the mRNA and protein expression of adiponectin in epididymal and subcutaneous fat depots were significantly increased in hypertensive rats. Adiponectin mRNA levels were strongly associated with PPARgamma mRNA levels in both epididymal (r=0.54, P<0.05) and subcutaneous (r=0.93, P<0.0001) fat. The expression of AdipoR1 and AdipoR2, acetyl-CoA carboxylase (ACC), as well as carnitine palmitoyl transferase 1 (CPT1), were increased in skeletal muscle of SHR. These changes were not observed in the liver of SHR. In addition, in spite of the hyperadiponectinemia, SHR showed similar activation of AMP-activated protein kinase (AMPK) and a lower phosphorylation degree of its downstream ACC in liver and skeletal muscle. Accordingly, SHR exhibited a significant increase in intrahepatic (approximately 40%) and intramyocellular (approximately 60%) lipid accumulation.


CONCLUSIONS
These findings suggest that dysregulation of the adiponectin downstream effectors contributes to increased intrahepatic and intramyocellular triglycerides in SHR. Hyperadiponectinemia together with overexpression of adiponectin receptors in skeletal muscle may reflect a defective compensatory mechanism to overcome adiponectin resistance in hypertensive rats.
Rodríguez
Amaia
A
Clínica Universitaria de Navarra, University of Navarra, Pamplona, Spain.
Catalán
Victoria
V
Becerril
Sara
S
Gil
María Jesús
MJ
Mugueta
Carmen
C
Gómez-Ambrosi
Javier
J
Frühbeck
Gema
G