GRP78 rescues the ABCG5 ABCG8 sterol transporter in db/db mice.

ABSTRACT:

Objective

Mice lacking leptin (ob/ob) or its receptor (db/db) are obese, insulin resistant, and have reduced levels of biliary cholesterol due, in part, to reduced levels of hepatic G5G8. Chronic leptin replacement restores G5G8 abundance and increases biliary cholesterol concentrations, but the molecular mechanisms responsible for G5G8 regulation remain unclear. In the current study, we used a series of mouse models to address potential mechanisms for leptin-mediated regulation of G5G8.

Methods and results

We acutely replaced leptin in ob/ob mice and deleted hepatic leptin receptors in lean mice. Neither manipulation altered G5G8 abundance or biliary cholesterol. Similarly, hepatic vagotomy had no effect on G5G8. Alternatively, G5G8 may be decreased in ob/ob and db/db mice

SUBMITTER: Wang Y 

PROVIDER: S-EPMC4609626 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature