Defective lipid delivery modulates glucose tolerance and metabolic response to diet in apolipoprotein E-deficient mice.
OBJECTIVE
Apolipoprotein E (ApoE) regulates plasma lipid levels via modulation of lipolysis and serving as ligand for receptor-mediated clearance of triglyceride (TG)-rich lipoproteins. This study tested the impact of modulating lipid delivery to tissues on insulin responsiveness and diet-induced obesity.


METHODS
ApoE(+/+) and apoE(-/-) mice were placed on high-fat-high-sucrose diabetogenic diet or control diet for 24 weeks. Plasma TG clearance, glucose tolerance, and tissue uptake of dietary fat and glucose were assessed.


RESULTS
Plasma TG clearance and lipid uptake by adipose tissue were impaired, whereas glucose tolerance was improved in control diet-fed apoE(-/-) mice compared with apoE(+/+) mice after an oral lipid load. Fat mass was reduced in apoE(-/-) mice compared with apoE(+/+) mice under both dietary conditions. The apoE(-/-) mice exhibited lower body weight and insulin levels than apoE(+/+) mice when fed the diabetogenic diet. Glucose tolerance and uptake by muscle and brown adipose tissue (BAT) was also improved in mice lacking apoE when fed the diabetogenic diet. Indirect calorimetry studies detected no difference in energy expenditure and respiratory quotient between apoE(+/+) and apoE(-/-) mice on control diet. Energy expenditure and uncoupling protein-1 expression in BAT were slightly but not significantly increased in apoE(-/-) mice on diabetogenic diet.


CONCLUSIONS
These results demonstrated that decreased lipid delivery to insulin-sensitive tissues improves insulin sensitivity and ameliorates diet-induced obesity.
Hofmann
Susanna M
SM
Department of Pathology and Laboratory Medicine, Genome Research Institute (ML0507), University of Cincinnati, 2120 E. Galbraith Rd., Cincinnati, OH 45237, USA.
Perez-Tilve
Diego
D
Greer
Todd M
TM
Coburn
Beth A
BA
Grant
Erin
E
Basford
Joshua E
JE
Tschöp
Matthias H
MH
Hui
David Y
DY
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D001786:Blood Glucose / Q000378:metabolism; D003847:Deoxyglucose / Q000378:metabolism; D003927:Diet, Diabetic; D004734:Energy Metabolism; D005951:Glucose Tolerance Test; D008055:Lipids / Q000097:blood*; D008074:Lipoproteins / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014280:Triglycerides / Q000097:blood; D014316:Tritium
D001057:Apolipoproteins E; D001786:Blood Glucose; D008055:Lipids; D008074:Lipoproteins; D014280:Triglycerides; D014316:Tritium; D003847:Deoxyglucose