Changes in adiponectin, its receptors and AMPK activity in tissues of diet-induced diabetic mice.
OBJECTIVE
A high-fat and high-sucrose diet (HFHSD) is usually used to induce type 2-like diabetes in animal models. We investigated the effect of HFHSD on serum and tissue levels of adiponectin, its receptors and AMP-activated protein kinase (AMPK) activity in adipose tissue, skeletal muscle and the liver.


METHODS
C57Bl/6 male mice were fed either a standard diet or an HFHSD for four and 16 weeks, during which time glucose and insulin tolerance tests were performed.


RESULTS
After four weeks, the HFHSD-fed mice were obese and glucose-intolerant and, after 16 weeks, they were obese and diabetic. In general, four weeks of HFHSD feeding did not modify either circulating or tissue adiponectin levels, nor adiponectin receptors or AMPK activity in the tissues studied. A significant increase of circulating adiponectin was observed after 16 weeks of HFHSD feeding, whereas adiponectin expression was decreased in adipose tissue. Muscle expression of adiponectin was increased at 16 weeks in terms of both mRNA and protein levels, and correlated to adipose-specific gene expression. However, AdipoR1 mRNA levels and AMPK activity were decreased in muscle at 16 weeks, suggesting decreased sensitivity to adiponectin in the muscle of diabetic mice. Finally, liver adiponectin expression was detectable only at protein levels and was increased in HFHSD mice at 16 weeks, suggesting "contamination" by circulating adiponectin. AdipoR2 mRNA levels were significantly decreased, whereas AMPK was increased, in the liver at 16 weeks.


CONCLUSIONS
Overall, our data suggest that HFHSD-induced diabetes is not associated with adiponectin deficiency, but with tissue-specific defects of adiponectin-receptor expression and AMPK activity.
Bonnard
C
C
Inserm, U870, IFR62, 165, chemin-du-grand-Revoyet, 69600 Oullins, France.
Durand
A
A
Vidal
H
H
Rieusset
J
J
D000263:Adenylate Kinase / Q000097:blood / Q000378:metabolism*; D052242:Adiponectin / Q000097:blood / Q000378:metabolism*; D000821:Animal Feed; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000209:etiology / Q000378:metabolism*; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D054419:Receptors, Adiponectin / Q000097:blood / Q000378:metabolism*; D013395:Sucrose
D052242:Adiponectin; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D054419:Receptors, Adiponectin; C475421:adiponectin receptor 2, mouse; D013395:Sucrose; D007041:Hypoxanthine Phosphoribosyltransferase; D000263:Adenylate Kinase