Reduced intestinal fat absorptive capacity but enhanced susceptibility to diet-induced fatty liver in mice heterozygous for ApoB38.9 truncation.
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. Because 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 apob(38.9/38.9) 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 HF diet. Thus the FHBL mice are more susceptible to diet-induced fatty liver despite relatively reduced intestinal TG absorption capacity on a HF diet.
Lin
Xiaobo
X
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Yue
Pin
P
Xie
Yan
Y
Davidson
Nicholas O
NO
Sakata
Nobuhiro
N
Ostlund
Richard E
RE
Chen
Zhouji
Z
Schonfeld
Gustav
G
D000818:Animals; D001055:Apolipoproteins B / Q000235:genetics*; D001835:Body Weight; D004041:Dietary Fats / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006579:Heterozygote; D007408:Intestinal Absorption / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D013230:Stearoyl-CoA Desaturase / Q000235:genetics; D014280:Triglycerides / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics
D001055:Apolipoproteins B; D004041:Dietary Fats; D014280:Triglycerides; D019014:fas Receptor; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase