Submitted on July 13, 2004
Accepted on March 10, 2005
Reduced Intestinal Fat Absorptive Capacity but Enhanced Susceptibility to Diet-induced Fatty Liver in Mice Heterozygous for ApoB38.9 Truncation
Xiaobo Lin1, Pin Yue1, Yan Xie1, Nicholas O. Davidson1, Nobuhiro Sakata1, Richard E Ostlund, Jr.1, Zhouji Chen1, and Gustav Schonfeld1*
1 Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
* To whom correspondence should be addressed. E-mail: gschonfe{at}wustl.edu.
Fatty liver is prevalent in apolipoprotein B (apoB)-defective familial
hypobetalipoproteinemia (FHBL). Similar to humans, mouse models of FHBL produced
by gene targeting [apob+/38.9], manifest low plasma cholesterol and increased hepatic
triglycerides [TG] even on a chow diet due to impaired hepatic VLDL-TG secretive
capacity. Since apoB truncations shorter than apoB48 are expressed in the intestine,
we examined whether FHBL mice may have limited capacity for intestinal dietary TG
absorption. In addition, we investigated whether FHBL mice are more susceptible to
diet-induced hepatic TG accumulation. Fat absorption capacity was impaired in
apoB38.9 mice in a gene dose-dependent manner. Relative fractional fat absorption
coefficients for apob+/+, apob+/38.9, and apob38.9/38.9 were 1.00, 0.96, and 0.71,
respectively. To raise hepatic TG we fed high-fat [HF] and low-fat [LF] pellets. Hepatic
TG level was observed in rank order: HF > LF > chow. On both LF and HF, liver TG
level was higher in the apob+/38.9 than in apob+/+. Hepatic TG secretion remained
impaired in the apob+/38.9 on the high-fat diet. Thus, the FHBL mice are more
susceptible to diet-induced fatty liver despite relatively reduced intestinal TG absorption
capacity on a high-fat diet.
