Metabolism of high density lipoprotein apolipoprotein A-I and cholesteryl ester in insulin resistant dog: a stable isotope study.
OBJECTIVE
In reverse cholesterol transport (RCT), hepatic Scavenger Receptor class B type I (SR-BI) plays an important role by mediating the selective uptake of high-density lipoprotein cholesteryl ester (HDL-CE). However, little is known about this antiatherogenic mechanism in insulin resistance. HDL-CE selective uptake represents the main process for HDL-CE turnover in dog, a species lacking cholesteryl ester transfer protein activity. We therefore investigate the effects of diet induced insulin resistance on RCT.


METHODS
Five beagle dogs, in healthy and insulin resistant states, underwent a primed constant infusion of [1,2(13)C(2)]acetate and [5,5,5-(2)H(3)]leucine, as labelled precursors of CE and apolipoprotein (apo) A-I, respectively. Data were analysed using modelling methods.


RESULTS
HDL-apo A-I concentration did not change in insulin resistant state but apo A-I absolute production rate (APR) and fractional catabolic rate (FCR) were both higher (2.2- and 2.4-fold, respectively, p < 0.05). HDL-CE levels were lower (1.2-fold, p < 0.05). HDL-CE APR and FCR were both lower (2.3- and 2-fold, respectively, p < 0.05), as well as selective uptake (2.6-fold, p < 0.05).


CONCLUSIONS
Lower HDL-CE selective uptake suggests that RCT is impaired in obese insulin resistant dog.
Briand
F
F
Bailhache
E
E
Nguyen
P
P
Krempf
M
M
Magot
T
T
Ouguerram
K
K
D000818:Animals; D016632:Apolipoprotein A-I / Q000097:blood*; D001692:Biological Transport; D002788:Cholesterol Esters / Q000097:blood*; D004285:Dogs; D007333:Insulin Resistance; D008297:Male; D009765:Obesity / Q000097:blood*
D016632:Apolipoprotein A-I; D002788:Cholesterol Esters