Metabolism and short-term metabolic effects of conjugated linoleic acids in rat hepatocytes.
Metabolic fate and short-term effects of a 1:1 mixture of cis-9,trans-11 and trans-10,cis-12-conjugated linoleic acids (CLA), compared to linoleic acid (LA), on lipid metabolism was investigated in rat liver. In isolated mitochondria CLA-CoA were poorer substrates than LA-CoA for carnitine palmitoyltransferase-I (CPT-I) activity. However, in digitonin-permeabilized hepatocytes, where interactions among different metabolic pathways can be simultaneously investigated, CLA induced a remarkable stimulatory effect on CPT-I activity. This stimulation can be ascribed to a reduced malonyl-CoA level in turn due to inhibition of acetyl-CoA carboxylase (ACC) activity. The ACC/malonyl-CoA/CPT-I system can therefore represent a coordinate control by which CLA may exert effects on the partitioning of fatty acids between esterification and oxidation. Moreover, the rate of oxidation to CO2 and ketone bodies was significantly higher from CLA; peroxisomes rather than mitochondria were responsible for this difference. Interestingly, peroxisomal acyl-CoA oxidase (AOX) activity strongly increased by CLA-CoA compared to LA-CoA. CLA, metabolized by hepatocytes at a higher rate than LA, were poorer substrates for cellular and VLDL-triacylglycerol (TAG) synthesis. Overall, our results suggest that increased fatty acid oxidation with consequent decreased fatty acid availability for TAG synthesis is a potential mechanism by which CLA reduce TAG level in rat liver.
Priore
Paola
P
Laboratory of Biochemistry, Department of Biological and Environmental Sciences and Technologies, University of Salento, Via Prov.le Lecce-Monteroni, 73100 Lecce, Italy.
Giudetti
Anna M
AM
Natali
Francesco
F
Gnoni
Gabriele V
GV
Geelen
Math J H
MJ
D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D042962:Acyl-CoA Oxidase; D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism*; D044243:Linoleic Acids, Conjugated / Q000378:metabolism*; D008055:Lipids / Q000737:chemistry; D008099:Liver / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D010088:Oxidoreductases / Q000378:metabolism; D020675:Peroxisomes / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D005227:Fatty Acids; D044243:Linoleic Acids, Conjugated; D008055:Lipids; D010088:Oxidoreductases; C107176:peroxisomal acyl-CoA oxidase; D042962:Acyl-CoA Oxidase; D000103:Acetyl-CoA Carboxylase