Down-regulation of lipoprotein lipase and VLDL receptor in rats with focal glomerulosclerosis.
BACKGROUND
Patients and animals with nephrotic syndrome and those with chronic renal failure (CRF) often exhibit hypertriglyceridemia and impaired very low-density lipoprotein (VLDL) clearance. Imai rats that were originally derived from Sprague-Dawley rats develop spontaneous proteinuria, hyperlipidemia, progressive renal insufficiency and histologic changes of focal glomerulosclerosis (FGS), closely resembling human FGS. This study was undertaken to test the hypothesis that elevation of plasma triglyceride and VLDL concentrations in the Imai rats is associated with deficiency of lipoprotein lipase (LPL) and VLDL receptor which are the main pathways of triglyceride-rich lipoprotein clearance.


METHODS
Male Imai and Sprague-Dawley control rats were fed regular rat chow and studied at 10 and 34 weeks of age. Tissue LPL and VLDL-r protein abundance (Western analysis) and post-heparin lipolytic activity were determined.


RESULTS
At 10 weeks of age, Imai rats showed mild proteinuria, moderate hyperlipidemia, normal creatinine clearance and blood pressure. By 34 weeks of age, the study animal exhibited severe proteinuria, marked hyperlipidemia, significant renal insufficiency and hypertension. This was associated with a severe progressive reduction in skeletal muscle and adipose tissue LPL and VLDL-r protein abundance and depressed plasma post heparin, lipolytic activity.


CONCLUSIONS
Progressive hyperlipidemia in the Imai rats with spontaneous FGS is accompanied by severe combined LPL and VLDL-r deficiencies that can, in part, account for the associated hypertriglyceridemia and elevated plasma VLDL concentrations.
Sato
Tadashi
T
Department of Pediatrics, Saga Medical School Saga-City, Saga, Japan.
Liang
Kaihui
K
Vaziri
Nosratola D
ND
D000818:Animals; D015536:Down-Regulation / Q000502:physiology; D005923:Glomerulosclerosis, Focal Segmental / Q000378:metabolism*; D015228:Hypertriglyceridemia / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000172:deficiency / Q000378:metabolism*; D008297:Male; D009404:Nephrotic Syndrome / Q000378:metabolism; D011507:Proteinuria / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D011973:Receptors, LDL / Q000172:deficiency / Q000378:metabolism*; D051437:Renal Insufficiency / Q000378:metabolism
D011973:Receptors, LDL; C036053:VLDL receptor; D008071:Lipoprotein Lipase