Decreased liver triglyceride content in adult rats exposed to protein restriction during gestation and lactation: role of hepatic triglyceride utilization

Abstract

We have previously demonstrated that protein restriction throughout gestation and lactation reduces liver triglyceride content in adult rat offspring. However, the mechanisms mediating the decrease in liver triglyceride content are not understood. The aim of the current study was to use a new group of pregnant animals and their offspring and determine the contribution of increased triglyceride utilization via the hepatic fatty-acid oxidation and triglyceride secretory pathways to the reduction in liver triglyceride content. Pregnant Sprague-Dawley rats received either a control or a low protein diet throughout pregnancy and lactation. Pups were weaned onto laboratory chow on day 28 and killed on day 65. Liver triglyceride content was reduced in male, but not female, low-protein offspring, both in the fed and fasted states. The reduction was accompanied by a trend towards higher liver carnitine palmitoyltransferase-1a activity, suggesting increased fatty-acid transport into the mitochondrial matrix. However, medium-chain acyl coenzyme A dehydrogenase activity within the mitochondrial matrix, expression of nuclear peroxisome proliferator activated receptor-α, and plasma levels of β-hydroxybutyrate were similar between low protein and control offspring, indicating a lack of change in fatty-acid oxidation. Hepatic triglyceride secretion, assessed by blocking peripheral triglyceride utilization and measuring serum triglyceride accumulation rate, and the activity of microsomal transfer protein, were similar between low protein and control offspring. Because enhanced triglyceride utilization is not a significant contributor, the decrease in liver triglyceride content in male low-protein offspring is likely due to alterations in liver fatty-acid transport or triglyceride biosynthesis.

Keywords: fatty-acid oxidation; hepatic triglyceride secretion; liver glycogen content; liver triglyceride content.

Figure 1

Liver triglyceride content in 65 day old control and low protein offspring in the fed and fasted states. A. Males B. Females. Data were analyzed by two-way split plot ANOVA using maternal diet (control or low protein) and feed status (fed or fasted) as the main factors followed by Bonferroni multiple comparison test. n = 9 – 10. * P<0.05 compared to liver triglyceride content in control group within the same feed status. # P<0.05 compared to liver triglyceride content in the fed state within the same group.

Figure 2

Liver CPT-1a activity in 65 day old control and low protein offspring in the fed and fasted states. A. Males B. Females. For details of statistical analyses refer methods and legend of Figure 1. n = 9 – 10. # P<0.05 compared to activity in the fed state within the same group.

Figure 3

Liver MCAD activity in 65 day old control and low protein offspring in the fed and fasted states. A. Males B. Females. For details of statistical analyses refer methods and legend of Figure 1. n = 9 – 10. # P<0.05 compared to activity in the fed state within the same group.

Figure 4

mRNA expression of PPAR-α in 65 day old control and low protein male offspring in the fed and fasted states. A. Males B. Females. For details of statistical analyses refer methods and legend of Figure 1. n = 8 – 10. # P<0.05 compared to activity in the fed state within the same group.

Figure 5

Liver glycogen content in 65 day old control and low protein offspring in the fed and fasted states. A. Males B. Females. For details of statistical analyses refer methods and legend of Figure 1. n = 9 – 10. # P<0.05 compared to liver glycogen content in the fed state within the same group.