The role of lipogenesis in the development of uremic hyperlipidemia.
BACKGROUND
It is well documented that hypertriglyceridemia in renal failure mostly is a result of impaired plasma triglyceride (TG) removal. However, the role of TG production in its development is obscure. Therefore, our attention was given to the gene expression of lipogenic enzymes participating in TG biosynthesis.


METHODS
We measured some lipogenic enzyme activities, protein abundance (Western blot analysis), and messenger RNA level (Northern blot analysis) in liver and epididymal white adipose tissue (WAT) of rats with surgically induced renal failure (two-stage subtotal nephrectomy). Simultaneously, plasma TG and very low-density lipoprotein (VLDL) concentrations in uremic animals were determined.


RESULTS
An increase in plasma TG and VLDL concentrations in rats with renal failure was observed. It was associated with an increase in fatty acid synthase and adenosine triphosphate-citrate lyase (ACL) gene expression in liver and WAT. Moreover, increased activities of malic enzyme, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase were found.


CONCLUSIONS
Results of the present study provide some evidence that the accumulation of TG-rich lipoproteins in renal insufficiency could be related in part to increased lipogenic enzyme gene expression and, consequently, TG overproduction.
Rutkowski
Boleslaw
B
Department of Nephrology, Medical University of Gdansk, Poland. bolo@amedec.amg.gda.pl
Szolkiewicz
Marek
M
Korczynska
Justyna
J
Sucajtys
Elzbieta
E
Stelmanska
Ewa
E
Nieweglowski
Tomasz
T
Swierczynski
Julian
J
D001275:ATP Citrate (pro-S)-Lyase / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000273:Adipose Tissue / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern / Q000379:methods / Q000706:statistics & numerical data; D015153:Blotting, Western / Q000379:methods / Q000706:statistics & numerical data; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics / Q000502:physiology; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D006949:Hyperlipidemias / Q000097:blood / Q000201:enzymology* / Q000378:metabolism* / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000097:blood / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008099:Liver / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism; D008291:Malate Dehydrogenase / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D009392:Nephrectomy; D010734:Phosphogluconate Dehydrogenase / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D008055:Lipids; D012333:RNA, Messenger; D008291:Malate Dehydrogenase; C031917:malate dehydrogenase (oxaloacetate-decarboxylating) (NADP+); D010734:Phosphogluconate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase; D001275:ATP Citrate (pro-S)-Lyase