Mechanisms of enhanced carbohydrate and lipid metabolism in adipose tissue in uremia.
OBJECTIVE
Hyperlipidemia is a permanent finding in advanced renal failure. It is supposed to be responsible for the accelerated arteriosclerosis and cardiovascular complications observed in patients with that disease. The background is partially determined, however, our knowledge in this matter is not yet satisfactory.


METHODS
This study is based on the experimental rat model of chronic renal failure (CRF). Considering white adipose tissue (WAT) lipogenesis upregulation in CRF, along with the determination of acetyl coenzyme A carboxylase (ACC) and fatty acid synthase (FAS) genes expression, we have measured WAT gene expression for sterol regulatory binding protein 1 (SREBP-1) at the level of protein mass and mRNA abundance. Furthermore, we have determined glucose uptake, glucose-to-CO 2 conversion rate, and glucose translocator (GLUT-4) gene expression in WAT.


RESULTS
Upregulation of both FAS and ACC gene expression was found in WAT of CRF rats. It was accompanied by WAT SREBP-1 gene overexpression. Moreover, we have observed the increased glucose uptake, glucose to CO 2 conversion rate, and GLUT-4 gene expression in WAT of CRF rats in comparison with controls.


CONCLUSIONS
SREBP-1 gene overexpression may contribute to enhanced lipogenesis upregulation in WAT of CRF rats. It is not excluded that the increased WAT glucose metabolism activity is also induced by this mechanism, although there is no evidence currently to that end. We hypothesize that the increased WAT lipogenesis capacity could be a part of mechanism(s) leading to CRF-induced hyperlipidemia.
Szolkiewicz
Marek
M
Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdansk, Gdansk, Poland.
Sucajtys
Elzbieta
E
Wolyniec
Wojciech
W
Rutkowski
Przemyslaw
P
Stelmanska
Ewa
E
Korczynska
Justyna
J
Swierczynski
Julian
J
Rutkowski
Boleslaw
B
D000103:Acetyl-CoA Carboxylase / Q000235:genetics; D000273:Adipose Tissue / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D050260:Carbohydrate Metabolism; D002467:Cell Nucleus / Q000737:chemistry; D004195:Disease Models, Animal; D064429:Fatty Acid Synthases / Q000235:genetics; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000235:genetics; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D050356:Lipid Metabolism; D008297:Male; D008861:Microsomes / Q000737:chemistry; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics; D015854:Up-Regulation; D014511:Uremia / Q000378:metabolism*
D051275:Glucose Transporter Type 4; D012333:RNA, Messenger; C495694:Slc2a4 protein, rat; D051780:Sterol Regulatory Element Binding Protein 1; D064429:Fatty Acid Synthases; D000103:Acetyl-CoA Carboxylase; D005947:Glucose