Liver fat accumulation may be dissociated from adiposity gain in ovariectomized rats

Abstract

Objective The purpose of the present study was to establish a model of rats prone and resistant to intra-abdominal fat accumulation in response to ovariectomy (Ovx-P and Ovx-R) and to determine its relationship with molecular biomarkers.

Design Two experiments were conducted in which female rats were either sham-operated (Sham) or ovariectomized (Ovx). In the first experiment, ovariectomized rats were stratified into three tertiles based on intra-abdominal adipose tissue mass. To strengthen the Ovx-P/Ovx-R model, we conducted a second experiment in which the numbers of rats in each group were extended and in which different molecular markers were measured. At the end of a 6–8-week period, ovariectomized rats that displayed the lower abdominal fat accumulation (lower tertile) were labelled as Ovx-R and those in the upper tertile as Ovx-P.

Results Ovx-R rats displayed similar abdominal fat gain to Sham rats whereas Ovx-P rats depicted abdominal fat mass twice as high as that of Sham and Ovx-R rats. Despite the difference in abdominal adiposity, liver fat content was ∼50% higher (p < 0.01) in both Ovx-R and Ovx-P rats compared to Sham rats. In addition, both Ovx-R and Ovx-P rats depicted higher HOMA-IR scores (p < 0.05) and lower (p < 0.01) hepatic gene expression of leptin receptor-b and -e, microsomal transfer protein (MTP), and diacylglycerol acyltransferase-2 (DGAT-2) compared to Sham rats.

Conclusion The present findings indicate that estrogen withdrawal-induced hepatic steatosis and associated insulin resistance may be dissociated from abdominal fat accumulation and suggest that a decrease in leptin action through a down-regulation of leptin receptors and a decrease in very low density lipoprotein production through a down-regulation of MTP and DGAT-2 may be factors responsible for this observation in the absence of peripheral fat gain.

Key words::

• HEPATIC STEATOSIS
• ADIPOSE TISSUE
• MICROSOMAL TRANSFER PROTEIN
• OB RECEPTORS
• DGAT

Conflict of interest Siham Yasari is presently employed by the Canadian Institutes of Health Research and declares no conflict of interest.

Source of funding This work was supported by grants from the Canadian Institutes of Health Research (RRL, DP, JML; T 0602 145.02) and the Natural Sciences and Engineering Research Council of Canada (JML; 7594).