Triglyceride-lowering effect of respiratory uncoupling in white adipose tissue.
OBJECTIVE
Hypolipidemic drugs such as bezafibrate and thiazolidinediones are known to induce the expression of mitochondrial uncoupling proteins (UCPs) in white adipose tissue. To analyze the potential triglyceride (TG)-lowering effect of respiratory uncoupling in white fat, we evaluated systemic lipid metabolism in aP2-Ucp1 transgenic mice with ectopic expression of UCP1 in adipose tissue.


METHODS
Hemizygous and homozygous transgenic mice and their nontransgenic littermates were fed chow or a high-fat diet for up to 3 months. Total TGs, nonesterified fatty acids, and the composition of plasma lipoproteins were analyzed. Hepatic TG production was measured in mice injected with Triton WR1339. Uptake and the use of fatty acids were estimated by measuring adipose tissue lipoprotein lipase activity and fatty acid oxidation, respectively. Adipose tissue gene expression was assessed by quantitative reverse transcriptase-polymerase chain reaction.


RESULTS
Transgene dosage and the high-fat diet interacted to markedly reduce plasma TGs. This was reflected by decreased concentrations of very-low-density lipoprotein particles in the transgenic mice. Despite normal hepatic TG secretion, the activity of lipoprotein lipase in epididymal fat was enhanced by the high-fat diet in the transgenic mice in a setting of decreased re-esterification and increased in situ fatty acid oxidation.


CONCLUSIONS
Respiratory uncoupling in white fat may lower plasma lipids by enhancing their in situ clearance and catabolism.
Rossmeisl
Martin
M
Department of Adipose Tissue Biology, Institute of Physiology, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague 4, Czech Republic.
Kovar
Jan
J
Syrovy
Ivo
I
Flachs
Pavel
P
Bobkova
Dagmar
D
Kolar
Frantisek
F
Poledne
Rudolf
R
Kopecky
Jan
J
D000273:Adipose Tissue / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics; D004041:Dietary Fats / Q000008:administration & dosage; D004822:Epididymis; D005227:Fatty Acids / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015870:Gene Expression; D006720:Homozygote; D007473:Ion Channels; D007657:Ketone Bodies / Q000096:biosynthesis; D008071:Lipoprotein Lipase / Q000378:metabolism; D008074:Lipoproteins / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins; D010084:Oxidation-Reduction; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000235:genetics; D014280:Triglycerides / Q000096:biosynthesis / Q000097:blood*; D000071256:Uncoupling Protein 1
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D004041:Dietary Fats; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D007473:Ion Channels; D007657:Ketone Bodies; D008074:Lipoproteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D014280:Triglycerides; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D008071:Lipoprotein Lipase; D010729:Phosphoenolpyruvate Carboxykinase (GTP)