Prevention of hyperphagia prevents ovariectomy-induced triacylglycerol accumulation in liver, but not plasma

Abstract

Menopause is associated with higher plasma and liver triacylglycerol (TAG) and increased risk for cardiovascular disease. Lowering TAG in menopause may be beneficial; however, the mechanism underlying menopause-induced TAG accumulation is not clear. Ovariectomy is a model for menopause and is associated with metabolic alterations and hyperphagia. This study investigated the role of hyperphagia in ovariectomy-induced increases in blood and tissue TAG, as well as differences in lipid metabolism enzymes and resting metabolic measures. It was hypothesized that prevention of hyperphagia would restore blood and tissue TAG, enzyme expression, and metabolic measures to eugonadal levels. Ovariectomized rats were fed ad libitum (OVX + AL) or pair-fed (OVX + PF) relative to sham-operated rats (SHAM) to prevent hyperphagia. OVX + AL had higher TAG concentrations in liver and plasma than SHAM (60% and 50%, respectively), and prevention of hyperphagia in OVX + PF normalized TAG concentrations to SHAM levels in liver, but not plasma. OVX + AL also had 141% higher hepatic stearoyl-CoA desaturase 1 which was almost completely normalized to SHAM levels by pair-feeding, suggesting normalization of hepatic lipid storage. In contrast, skeletal muscle carnitine palmitoyl transferase 1 was 40% lower in OVX + AL than SHAM and was intermediate in OVX + PF, suggesting lower muscle fatty acid oxidation that may underlie the higher plasma TAG in OVX. No differences were seen in energy expenditure, VO2, or VCO2. Overall, this study indicates that prevention of hyperphagia resulting from ovarian hormone withdrawal normalizes hepatic TAG to eugonadal levels but has no effect on ovariectomy-induced increases in plasma TAG.