Hepatic VLDL-TG Production and MTP Gene Expression are Decreased in Ovariectomized Rats: Effects of Exercise Training

Abstract

The present study was designed to investigate the effects of estrogen withdrawal and exercise training on hepatic very low density lipoprotein-triglyceride (VLDL-TG) production and on expression of genes involved in hepatic VLDL synthesis in response to lipid infusion. Female Sprague-Dawley rats underwent ovariectomy (Ovx), sham surgery (Sham), and Ovx with 17β-estradiol supplementation (OvxE2) before being subdivided into sedentary (Sed) and trained (Tr) groups for 8 weeks. Exercise training consisted of continuous running on a rodent treadmill 5 times/wk. At the end of the 8-week period, all rats in the fasted state were intravenously infused with a 20% solution of Intralipid for 3-h followed by an injection of Triton WR-1339 to block lipoprotein lipase activity. Plasma TG accumulation was subsequently measured during 90 min to estimate VLDL-TG production. An additional control group consisting of Sham-Sed rats was infused with saline (0.9% NaCl). Estrogen withdrawal resulted in higher (p<0.01) liver fat accumulation concomitantly with lower (p<0.01) VLDL-TG production and lower mRNA and protein content of hepatic microsomal triglyceride transfer protein (MTP). All of these effects in Ovx rats were corrected with estrogen supplementation. Training in Ovx rats reduced (p<0.01) liver fat accumulation and further reduced (p<0.01) hepatic VLDL-TG production along with gene expression of MTP and diacylglycerol acyltransferase-2 (DGAT-2). It is concluded that VLDL-TG synthesis and/or secretion is decreased in Ovx rats probably via MTP regulation and that this decrease may constitute one of the factors involved in hepatic fat accumulation. The training effect on reducing VLDL production was independent of the estrogenic status.