Genetic background (C57BL/6J versus FVB/N) strongly influences the severity of diabetes and insulin resistance in ob/ob mice.
We studied the effects of genetic background on the phenotype of ob/ob mice, a model of severe obesity, insulin resistance, and diabetes caused by leptin deficiency. Despite a comparable degree of obesity and hyperinsulinemia, C57BL/6J ob/ob mice had much milder hyperglycemia and, surprisingly, normal circulating adiponectin levels despite still-prominent signs of insulin resistance. Hyperinsulinemic-euglycemic clamp revealed relatively less whole-body and muscle insulin resistance in C57BL/6J ob/ob mice, whereas liver insulin resistance tended to be more severe than in FVB/N ob/ob mice. C57BL/6J ob/ob mice had also more rapid clearance of circulating triglycerides and more severe hepatic steatosis. We suggest that strain-related distinction in lipid handling is the most important player in the differences in diabetic phenotype and insulin sensitivity, whereas the impact of circulating adiponectin levels on the overall phenotype of ob/ob mice is less important.
Haluzik
Martin
M
Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. mhalu@lf1.cuni.cz.
Colombo
Carlo
C
Gavrilova
Oksana
O
Chua
Streamson
S
Wolf
Nicole
N
Chen
Min
M
Stannard
Bethel
B
Dietz
Kelly R
KR
Le Roith
Derek
D
Reitman
Marc L
ML
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003920:Diabetes Mellitus / Q000235:genetics* / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism*; D004798:Enzymes / Q000235:genetics; D005260:Female; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics*; D008099:Liver / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity; D009767:Obesity, Morbid / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D012720:Severity of Illness Index; D013045:Species Specificity; D014280:Triglycerides / Q000378:metabolism
D001786:Blood Glucose; D004798:Enzymes; D007328:Insulin; D012333:RNA, Messenger; D014280:Triglycerides