Metabolism and short-term metabolic effects of conjugated linoleic acids in rat hepatocytes

Laboratory of Biochemistry, Department of Biological and Environmental Sciences and Technologies, University of Salento, Via Prov.le Lecce-Monteroni, 73100 Lecce, Italy.
Biochimica et Biophysica Acta (Impact Factor: 4.66). 11/2007; 1771(10):1299-307. DOI: 10.1016/j.bbalip.2007.08.005
Source: PubMed


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.

11 Reads
  • Source
    • "The cell precipitate was spun down, and supernatants were washed three times with light petroleum ether. ASP were subsequently extracted from the samples [36]. Total oxidation products were determined as the sum of radioactivity of CO2 plus ASP. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Growing evidence shows that, among triiodothyronine derivatives, 3,5 diiodo-L-thyronine (T(2)) plays an important role in energy metabolism and fat storage. In the present study, short-term effects of T(2) administration to hypothyroid rats on fatty acid oxidation rate and bioenergetic parameters were investigated. Within 1 h following T(2) injection, state 3 and state 4 respiration rates, which were reduced in hypothyroid mitochondria, were noticeably increased particularly in succinate- with respect to glutamate/malate-energized mitochondria. Maximal respiratory activity, observed when glutamate/malate/succinate were simultaneously present in the respiratory medium, was significantly stimulated by T(2) treatment. A T(2)-induced increase in respiratory rates was also observed when palmitoyl-CoA or L-palmitoylcarnitine were used as substrates. No significant change in respiratory control index and ADP/O ratio was observed. The activities of the mitochondrial respiratory chain complexes, especially Complex II, were increased in T(2)-treated rats. In the latter, Complex V activities, assayed in both ATP synthesis and hydrolysis direction, were enhanced. The rate of fatty acid oxidation, followed by conversion of [(14)C]palmitate to CO(2) and ketone bodies, was higher in hepatocytes isolated from T(2)-treated rats. This increase occurs in parallel with the raise in the activity of carnitine palmitoyltransferase-I, the rate limiting enzyme of fatty acid β-oxidation, assayed in situ in digitonin-permeabilized hepatocytes. Overall, these results indicate that T(2) rapidly increases the ability of mitochondria to import and oxidize fatty acids. An emerging idea in the literature is the ability of T(2) to reduce adiposity and dyslipidemia and to prevent the development in liver steatosis. The results of the present study, showing a rapid T(2)-induced increase in the ability of mitochondria to import and oxidize fatty acids, may contribute to understand the biochemical mechanisms of T(2)-metabolic effects.
    PLoS ONE 01/2013; 8(1):e52328. DOI:10.1371/journal.pone.0052328 · 3.23 Impact Factor
  • Source
    • "These activities of 13-oxo-ODA were similar to those of 9-oxo-ODA (data not shown). In addition, the activities of 13-oxo-ODA were similar to those of CLA, which is considered a functional nutrient that improves abnormalities of lipid metabolism by activating PPARα [16] and increasing fatty acid oxidation [33]. Thus, our findings suggest that 13-oxo-ODA, as a PPARα agonist, is also valuable for control of lipid metabolism, similar to 9-oxo-ODA and CLA. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Dyslipidemia is a major risk factor for development of several obesity-related diseases. The peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated transcription factor that regulates energy metabolism. Previously, we reported that 9-oxo-10,12-octadecadienoic acid (9-oxo-ODA) is presented in fresh tomato fruits and acts as a PPARα agonist. In addition to 9-oxo-ODA, we developed that 13-oxo-9,11-octadecadienoic acid (13-oxo-ODA), which is an isomer of 9-oxo-ODA, is present only in tomato juice. In this study, we explored the possibility that 13-oxo-ODA acts as a PPARα agonist in vitro and whether its effect ameliorates dyslipidemia and hepatic steatosis in vivo. In vitro luciferase assay experiments revealed that 13-oxo-ODA significantly induced PPARα activation; moreover, the luciferase activity of 13-oxo-ODA was stronger than that of 9-oxo-ODA and conjugated linoleic acid (CLA), which is a precursor of 13-oxo-ODA and is well-known as a potent PPARα activator. In addition to in vitro experiment, treatment with 13-oxo-ODA decreased the levels of plasma and hepatic triglycerides in obese KK-Ay mice fed a high-fat diet. In conclusion, our findings indicate that 13-oxo-ODA act as a potent PPARα agonist, suggesting a possibility to improve obesity-induced dyslipidemia and hepatic steatosis.
    PLoS ONE 02/2012; 7(2):e31317. DOI:10.1371/journal.pone.0031317 · 3.23 Impact Factor
  • Source
    • "The cell precipitate was spun down, and supernatants were washed three times with light petroleum ether. ASP were subsequently extracted from the samples as in [23]. Total oxidation products were determined as the sum of CO2 plus ASP. "
    [Show abstract] [Hide abstract]
    ABSTRACT: There is growing evidence that mitochondrial dysfunction, and more specifically fatty acid β-oxidation impairment, is involved in the pathophysiology of non-alcoholic steatohepatitis (NASH). The goal of the present study was to achieve more understanding on the modification/s of carnitinepalmitoyltransferase-I (CPT-I), the rate-limiting enzyme of the mitochondrial fatty acid β-oxidation, during steatohepatitis. A high fat/methionine-choline deficient (MCD) diet, administered for 4 weeks, was used to induce NASH in rats.We demonstrated that CPT-I activity decreased, to the same extent, both in isolated liver mitochondria and in digitonin-permeabilized hepatocytes from MCD-diet fed rats.At the same time, the rate of total fatty acid oxidation to CO(2) and ketone bodies, measured in isolated hepatocytes, was significantly lowered in treated animals when compared to controls. Finally, an increase in CPT-I mRNA abundance and protein content, together with a high level of CPT-I protein oxidation was observed in treated rats. A posttranslational modification of rat CPT-I during steatohepatitis has been here discussed.
    PLoS ONE 09/2011; 6(9):e24084. DOI:10.1371/journal.pone.0024084 · 3.23 Impact Factor
Show more