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Effect of conjugated linoleic acid on inhibition of prolyl hydroxylase 1 in hearts of mice.

ABSTRACT: Results from different trails have provided evidence of protective effects of cis-9,trans-11-conjugated linoleic acid (CLA) on cardiovascular diseases. But the inhibition of prolyl hydroxylase 1 (PHD1) associated with induction of hypoxia inducible factors (HIFs) by CLA in these protective effects has never been reported before. The objective of this study was to evaluate if the two predominant cis-9,trans-11 (c9, t11), trans-10,cis-12 (t10, c12) CLA isomers and mixture of these two isomers can inhibit PHD1 with induction of HIFs in myocardium in mice and subsequent effects on myocardium metabolism.CLA mixture and c9, t11 CLA inhibited PHD1 protein expression and increased the levels of protein and mRNA in HIF-2? in myocardium in mice. Meanwhile, CLA mixture and c9, t11 CLA also elevated the expression of HIF related transcriptional factors like PDK4 and PPAR?. The reprogramming of basal metabolism in myocardium in mice was shown on increasing of GLUT4 gene expression by c9, t11 CLA supplemented group. UCP2 was increased by CLA mixture and c9, t11 CLA for attenuating production of ROS.CLA mixture and c9, t11 CLA could inhibit PHD1 and induce HIF-2? in myocardium in mice, which is associated with upregulation of PDK4 by activation of PPAR?. This process also implies a reprogramming of basal metabolism and oxidative damage protection in myocardium in mice. All the effects shown in hearts of mice are due to c9, t11 CLA but not t10, c12 CLA.

SUBMITTER: Zhang J

PROVIDER: S-EPMC3295668 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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Effect of conjugated linoleic acid on inhibition of prolyl hydroxylase 1 in hearts of mice.

Zhang Jize J Li Defa D

Lipids in health and disease 20120207

<h4>Background</h4>Results from different trails have provided evidence of protective effects of cis-9,trans-11-conjugated linoleic acid (CLA) on cardiovascular diseases. But the inhibition of prolyl hydroxylase 1 (PHD1) associated with induction of hypoxia inducible factors (HIFs) by CLA in these protective effects has never been reported before. The objective of this study was to evaluate if the two predominant cis-9,trans-11 (c9, t11), trans-10,cis-12 (t10, c12) CLA isomers and mixture of the ...[more]

PMID: 22313584

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Project description:BackgroundThe individual genetic variations, as a response to diet, have recently caught the attention of several researchers. In addition, there is also a trend to assume food containing beneficial substances, or to supplement food with specific compounds. Among these, there is the conjugated linoleic acid (CLA), which has been demonstrated to reduce fat mass and to increase lean mass, even though its mechanism of action is still not known. We investigated the effect of CLA isomers (CLA c9,t11 and CLA t10,c12) on the proteomic profile of liver, adipose tissue, and muscle of mouse, with the aim of verifying the presence of a modification in fat and lean mass, and to explore the mechanism of action.MethodsC57/BL6 mice were fed for 2 months with different diets: (1) standard chow, (2) CLA c9,t11 diet, (3) CLA t10,c11 diet, (4) CLA isomers mixture diet, and (5) linoleic acid diet. The proteomic profile of liver, white adipose tissue, and muscle was investigated. Statistical significance of the spots with an intensity higher than twofold in expression compared to the control was tested using student's t test (two-tail).ResultsWe found that both isomers modulate the proteomic profiles of liver, adipose tissue, and muscle by different mechanisms of action. Liver steatosis is mostly due to the isomer CLA t10,c12, since it alters the expression of lipogenetic proteins; it acts also reducing the adipose tissue and increasing fatty acid oxidation in muscle. Conversely, CLA c9,t11 has no relevant effects on liver and adipose tissue, but acts mostly on muscle, where it enhances muscular cell differentiation.ConclusionsAdministration of CLA in humans has to be carefully personalized, since even considering the presence of a species-specific effect, adverse effects might occur on long-term supplementation. Here we demonstrated that, in mouse, CLA is effective in reducing fat mass, but it also induces liver steatosis. The increase of lean mass is linked to an induction of cell proliferation, which, on long-term supplementation, might also lead to adverse effects.

Project description:BackgroundInvestigation of microRNAs (miRNAs) in obesity, their genetic targets and influence by dietary modulators is of great interest because it may potentially identify novel pathways involved in this complex metabolic disorder and influence future therapeutic approaches. This study aimed to determine whether miRNAs expression may be influenced by conjugated linoleic acid (CLA), currently used to induce fat loss.Methodology/principal findingsWe determined retroperitoneal adipose tissue (rWAT) expression of five miRNAs related to adipocyte differentiation (miRNA-143) and lipid metabolism (miRNA-103 and -107) and altered in obesity (miRNA-221 and -222), using the TaqMan®MicroRNA Assay (Applied-Biosystems). In the first experiment, mice were fed with a standard fat diet and orally treated with sunflower oil (control group) and 3 or 10 mg CLA/day for 37 days. In the second experiment, mice were fed with a high fat diet for 65 days. For the first 30 days, mice received the same doses of CLA described above and, from that time onwards, animals received a double dose. Results showed that expression of selected miRNAs was modified in response to CLA treatment and metabolic status. Interestingly, a strong correlation was observed between miR-103 and -107 expression, as well as miR-221 and -222 in both experiments. Moreover, changes in miRNAs expression correlated with several adipocyte gene expressions: miR-103 and -107 correlated with genes involved in fatty acid metabolism whereas miR-221 and miR-222 correlated with the expression of adipocytokines. Regarding the minor changes observed in miR-143 expression, no differences in expression of adipogenic markers were observed.Conclusions/significanceAlthough elucidating the functional implications of miRNAs is beyond the scope of this study, these findings provide the first evidence that miRNAs expression may be influenced by dietary manipulation, reflecting or even contributing to the new metabolic state originated by CLA treatment.

Project description:Conjugated linoleic acids (CLAs) and conjugated linolenic acids (CLNAs) have gained significant attention due to their anticarcinogenic and lipid/energy metabolism-modulatory effects. However, their concentration in foodstuffs is insufficient for any therapeutic application to be implemented. From a biotechnological standpoint, microbial production of these conjugated fatty acids (CFAs) has been explored as an alternative, and strains of the genera Propionibacterium, Lactobacillus, and Bifidobacterium have shown promising producing capacities. Current screening research works are generally based on direct analytical determination of production capacity (e.g., trial and error), representing an important bottleneck in these studies. This review aims to summarize the available information regarding identified genes and proteins involved in CLA/CLNA production by these groups of bacteria and, consequently, the possible enzymatic reactions behind such metabolic processes. Linoleate isomerase (LAI) was the first enzyme to be described to be involved in the microbiological transformation of linoleic acids (LAs) and linolenic acids (LNAs) into CFA isomers. Thus, the availability of lai gene sequences has allowed the development of genetic screening tools. Nevertheless, several studies have reported that LAIs have significant homology with myosin-cross-reactive antigen (MCRA) proteins, which are involved in the synthesis of hydroxy fatty acids, as shown by hydratase activity. Furthermore, it has been suggested that CLA and/or CLNA production results from a stress response performed by the activation of more than one gene in a multiple-step reaction. Studies on CFA biochemical pathways are essential to understand and characterize the metabolic mechanism behind this process, unraveling all the gene products that may be involved. As some of these bacteria have shown modulation of lipid metabolism in vivo, further research to be focused on this topic may help us to understand the role of the gut microbiota in human health.

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Effect of conjugated linoleic acid on inhibition of prolyl hydroxylase 1 in hearts of mice.

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Effect of conjugated linoleic acid on inhibition of prolyl hydroxylase 1 in hearts of mice.

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