Differences in Cholesterol Metabolism, Hepato-Intestinal Aging, and Hepatic Endocrine Milieu in Rats as Affected by the Sex and Age

Abstract

Age and sex influence serum cholesterol levels, but the underlying mechanisms remain unclear. To investigate further, we measured cholesterol, precursors (surrogate synthesis markers), degradation products (oxysterols and bile acid precursors) in serum, the liver, jejunum, and ileum, as well as serum plant sterols (intestinal absorption markers) in male and female Wistar rats (4 and 24 months old). The analysis of histomorphometric and oxidative stress parameters (superoxide dismutase, catalase, glutathione-related enzyme activities, lipid peroxide, and protein carbonyl concentrations) in the liver and jejunum offered further insights into the age- and sex-related differences. The hepatic gene expression analysis included AR, ERα, and sex-specific growth hormone-regulated (Cyp2c11 and Cyp2c12) and thyroid-responsive (Dio1, Tbg, and Spot 14) genes by qPCR. We observed age-related changes in both sexes, with greater prominence in females. Aged females had significantly higher serum cholesterol (p p p p p p p p < 0.05) in the liver. Our study suggests that the more significant age-related increase in serum cholesterol in females is associated with poorer hepato-intestinal health and increased jejunal cholesterol absorption. The local increase in 27-hydroxycholesterol during aging might reduce the hepatoprotective effects of endogenous estrogen in the female liver.

Keywords

• sex differences
• age
• cholesterol metabolism
• oxidative stress
• liver
• small intestine