The liver plays a key role in whole body sterol accretion of the neonatal Golden Syrian hamster

Abstract

Neonates have a significant requirement for cholesterol. From -1 to 25 days of age, the liver accrues 6.9 mg cholesterol and the extra-hepatic tissues accrue 107.7 mg cholesterol in the hamster. It is currently unknown if each of these body compartments synthesizes their own cholesterol or if they have alternative source(s) of sterol. Using (3)H(2)O, in vivo hepatic sterol synthesis rates (per g liver per animal) increased between -1 and 5 days of age, decreased by 10 days of age, and increased again by 15 days of age. HMG-CoA reductase (HMGR) expression levels paralleled in vivo synthesis rates. Extra-hepatic sterol synthesis rates followed the same pattern as sterol synthesis rates in the liver. When sterol synthesis rates were converted to the mass of sterol synthesized per day, the liver synthesized 38.9 and the extra-hepatic tissues synthesized 63.9 mg cholesterol in the 26-day neonatal period. Comparing the amount of cholesterol accrued to that synthesized, one can conclude that the liver is a major source of sterol for the whole body during the neonatal period of the hamster. These results may help elucidate the cause(s) of reduced growth rates in neonates with liver disease or in neonates with compromised sterol synthesis rates.

Figure 1

Whole body and liver masses in neonatal and adult hamsters. Liver (A) and whole body (B) weights were measured in neonates from −1 to 25 days of age and in adult male (closed square) and female (open square) hamsters. Data are presented as means ± SEM in 12–30 animals. * depicts significant differences (P<0.05) from values at the previous age. Slopes for body weight was 2.34±0.07 (P<0.001) and for liver weight was 0.12±0.01 (P<0.001).

Figure 2

Plasma, VLDL/LDL, and liver cholesterol concentrations in neonatal and adult hamsters. Cholesterol concentrations were measured enzymatically in plasma (A; circles/squares) and VLDL/LDL FPLC fractions (A; triangles/diamonds) and by GLC in livers (B) and extra-hepatic tissues (C). Adult males were depicted by closed squares and diamonds and adult females by open squares and diamonds. Data are presented as means ± SEM in 3–18 animals (plasma), 4–30 animals (liver), or 7–15 animals (extra-hepatic tissues). Cholesterol contents in VLDL/LDL peaks were obtained from 3 pooled plasma samples. * depicts significant differences (P<0.05) from values at the previous age. Slopes for liver cholesterol concentration was −0.02±0.01 (P=0.022) and carcass cholesterol concentration was 0.02±0.01 (P=0.002).

Figure 3

Hepatic sterol synthesis rates in neonatal and adult hamsters. Sterol synthesis rates were measured in vivo using ³H₂O in neonates (−1 to 25 days of age) and adult males (closed square) and females (open square). Data are presented as nmol ³H₂O converted to sterol per h per g liver per animal (A) and per g liver per 100 g animal (B). Data are presented as means ± SEM in 6–16 animals. In Panel C, the relative expression levels of HMGR and β-actin are shown in hamsters of increasing ages (AD-adult male, AF-adult female). * depicts significant differences (P<0.05) from values at the previous age. Slope for sterol synthesis rate per 100 g animal was −616.3±105.9 (P<0.001).

Figure 4

Hepatic fatty acid synthesis rates in neonatal hamsters. Fatty acid synthesis rates were measured in vivo using ³H₂O in neonates (5 to 25 days of age). Data are presented as nmol ³H₂O converted to fatty acid per h per g liver. Data are presented as means ± SEM in 10–30 animals. * depicts significant differences (P<0.05) from values at the previous age. Slope for fatty acid synthesis rate was 3438±336 (P<0.001).

Figure 5

Extra-hepatic tissue sterol synthesis rates in neonatal and adult hamsters. Sterol synthesis rates were measured in vivo using ³H₂O in neonates (−1 to 25 days of age) and adult males (closed squares) and females (open squares). Data are presented as nmol ³H₂O converted to sterol per h per g tissue per animal (A) and per g tissue per 100 g animal (B). Data are presented as means ± SEM in 3–16 animals. * depicts significant differences (P<0.05) from values at the previous age. Slope for sterol synthesis rate per 100 g animal was −157.0±16.7 (P<0.001).

Figure 6

Net sterol balance in neonatal hamsters. The absolute masses of cholesterol synthesized and cholesterol accrued between −1 and 15 days of age or 16 to 25 days of age were calculated and presented for the liver (A) and extra-hepatic tissues (B) of neonatal hamsters.