Expression of apolipoprotein B in the kidney attenuates renal lipid accumulation.
The ability to produce apolipoprotein (apo) B-containing lipoproteins enables hepatocytes, enterocytes, and cardiomyocytes to export triglycerides. In this study, we examined secretion of apoB-containing lipoproteins from mouse kidney and its putative impact on triglyceride accumulation in the tubular epithelium. Mouse kidney expressed both the apoB and microsomal triglyceride transfer protein genes, which permit lipoprotein formation. To examine de novo lipoprotein secretion, kidneys from human apoB-transgenic mice were minced and placed in medium with (35)S-amino acids. Upon sucrose gradient ultracentrifugation of the labeled medium, fractions were analyzed by apoB immunoprecipitation. (35)S-Labeled apoB100 was recovered in approximately 1.03-1.04 g/ml lipoproteins (i.e. similar to the density of plasma low density lipoproteins). Immunohistochemistry of kidney sections suggested that apoB mainly is produced by tubular epithelial cells. ApoB expression in the kidney cortex was reduced approximately 90% in vivo by treating wild type mice with apoB-antisense locked nucleic acid oligonucleotide. Inhibition of apoB expression increased fasting-induced triglyceride accumulation in the kidney cortex by 20-25% (p = 0.008). Cholesterol stores were unaffected. Treatment with control oligonucleotides with 1 or 4 mismatching base pairs affected neither the triglyceride nor the cholesterol content of the kidney cortex. The results suggest that mammalian kidney secretes apoB100-containing lipoproteins. One biological effect may be to dampen excess storage of triglycerides in proximal tubule cells.
Krzystanek
Marcin
M
Department of Clinical Biochemistry, Rigshospitalet, DK-2100 Copenhagen.
Pedersen
Tanja Xenia
TX
Bartels
Emil Daniel
ED
Kjaehr
Jacob
J
Straarup
Ellen Marie
EM
Nielsen
Lars Bo
LB
D000818:Animals; D053299:Apolipoprotein B-100 / Q000235:genetics / Q000378:metabolism; D001055:Apolipoproteins B / Q000502:physiology*; D015153:Blotting, Western; D002784:Cholesterol / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014280:Triglycerides / Q000378:metabolism*
D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; C099283:Laptm4a protein, mouse; D008074:Lipoproteins; D026901:Membrane Transport Proteins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D014280:Triglycerides; D002784:Cholesterol