Conjugated linoleic acid and hepatic lipogenesis in mouse: role of the mitochondrial citrate carrier.
Conjugated linoleic acid (CLA) is able to reduce adiposity by affecting lipid metabolism. In particular, CLA administration to mice reduces body fat mass with a concomitant lipid accumulation in the liver. We investigated the effects of CLA on the activity of the mitochondrial citrate carrier (CIC), which is implicated in hepatic lipogenesis. The transport activity of the CIC, measured both in intact mitochondria and in the proteoliposomes, progressively increased with the duration of CLA feeding. An increase in the CIC activity of approximately 1.7-fold was found in 16 week CLA-treated mice with respect to control animals. A kinetic analysis showed a 1.6-fold increase in the V(max) of citrate transport but no change in the K(m) value. Western blot experiments revealed an increase of approximately 1.7-fold in the expression of CIC after CLA treatment. A strict correlation between the increase in CIC activity and the stimulation of the cytosolic lipogenic enzymes was also found. These data indicate that the CIC may play a role in the onset of hepatic steatosis in CLA-fed mice by supplying the carbon source for de novo fatty acid synthesis.
Ferramosca
Alessandra
A
Department of Sciences and Biological and Environmental Technologies, University of Lecce, 73100 Lecce, Italy.
Savy
Viviana
V
Conte
Laura
L
Colombo
Sara
S
Einerhand
Alexandra W C
AW
Zara
Vincenzo
V
D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D015152:Blotting, Northern; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019343:Citric Acid / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D064429:Fatty Acid Synthases / Q000378:metabolism; D005227:Fatty Acids / Q000096:biosynthesis / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D044243:Linoleic Acids, Conjugated / Q000008:administration & dosage / Q000494:pharmacology*; D008055:Lipids / Q000032:analysis / Q000097:blood; D050155:Lipogenesis / Q000187:drug effects*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D002352:Carrier Proteins; D005227:Fatty Acids; D044243:Linoleic Acids, Conjugated; D008055:Lipids; D012333:RNA, Messenger; C020723:citrate-binding transport protein; D019343:Citric Acid; D002334:Carnitine O-Palmitoyltransferase; D064429:Fatty Acid Synthases; D000103:Acetyl-CoA Carboxylase