Docosahexaenoic acid suppresses the expression of FoxO and its target genes

Chen, Yu-Jen; Chen, Chih-Chien; Li, Tsai-Kun; Wang, Pei-Hwa; Liu, Li-Ru; Chang, Fang-Ying; Wang, Ya-Chin; Yu, Yu-Hsiang; Lin, Shau-Ping; Mersmann, Harry J.; Ding, Shih‐Torng

doi:10.1016/j.jnutbio.2011.11.003

Cited by 45 publications

(37 citation statements)

References 57 publications

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“…Values are means ± SEM; n = 8 *P < 0.05, **P < 0.01, NS = not significant (Wilcoxon signed-rank test) as far as normal-weight, non-obese animals are concerned. Chen et al (2012) reported no significant effect of DHA oil in comparison with beef tallow on the body weight gain in weaned pigs, which agrees with the findings of the present experiment. Similarly, dietary intervention had no significant effect on either daily weight gain or the final live weight of rats fed a diet with fish oil and palm oil, respectively, in our previous experiment (Komprda et al 2014).…”

Section: Discussionsupporting

confidence: 93%

Tissue fatty acid deposition, plasma lipid and cytokine profile in pigs fed a diet with fish oil or palm oil

Komprda¹,

Rozikova²,

Vícenová³

et al. 2017

CZECH J ANIM SCI

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Komprda T., Rozíková V., Vícenová M., Procházková N., Ondráčková P., Pešková P., Faldyna M. (2017): Tissue fatty acid deposition, plasma lipid and cytokine profile in pigs fed a diet with fish oil or palm oil. Czech J. Anim. Sci., 62, 482-490.The present study tested a hypothesis concerning a favourable effect of dietary fish oil on the tissue polyunsaturated fatty acid (PUFA) deposition, and on plasma lipid and cytokine profile. Thirty-two pigs divided into two groups of 16 animals each were fed for 70 days a diet with 2.5% of fish oil (F) and palm oil (P), respectively. The content of PUFA n-3 in the liver, muscle (m. quadriceps femoris), and visceral adipose tissue (VAT) of the F-and P-pigs was 530 and 129, 84 and 19, 1365 and 191 mg/100 g of the fresh tissue, respectively (differences between dietary groups were significant at P < 0.01 in all tissues). Dietary fish oil in comparison with palm oil decreased (P < 0.05) total plasma cholesterol, but also desirable high-density lipoprotein cholesterol, and had no effect (P > 0.05) both on low-density lipoprotein cholesterol and triacylglycerols. Moreover, dietary fish oil increased (P < 0.05) expression of the genes coding for not only anti-inflammatory cytokines IL-10 (P < 0.01) and TGF-β1 (P < 0.05), but also for pro-inflammatory cytokines IL-6 (P < 0.01), IL-12, and TNF-α (P < 0.05) in the VAT, and increased (P < 0.05) the expression of the IL6 gene in the liver. On the other hand, no significant differences (P > 0.05) between the F-and P-pigs in plasma levels of any tested cytokine were found out. It was concluded that an effect of dietary fish oil on tissue fatty acid deposition is undeniable, but its effects on plasma markers related to the risk of chronic degenerative diseases require further research.

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Section: Discussionsupporting

confidence: 93%

Tissue fatty acid deposition, plasma lipid and cytokine profile in pigs fed a diet with fish oil or palm oil

Komprda¹,

Rozikova²,

Vícenová³

et al. 2017

CZECH J ANIM SCI

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“…Linoleic acid (C18:2n-6) as well as cis-4, 7, 10, 13, 16, 19-docosahexaenoic acid (C22:6n-3), which have been suggested to decrease obesity features [7,8], decreased significantly in this study. Mice under calorie restriction have shown increased expression of genes responsible of FA β-oxidation compared with ad libitum-fed controls [5], what may be implicated in the reduction of body fat after weight loss.…”

Section: Discusionmentioning

confidence: 49%

Metabolomics identifies changes in fatty acid and amino acid profiles in serum of overweight older adults following a weight loss intervention

et al. 2014

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3 AbstractThe application of metabolomics in nutritional research may be a useful tool to analyse and predict the response to a dietary intervention. The aim of this study was to examine metabolic changes in serum samples following exposure to an energy-restricted diet (-15% of daily energy requirements) over a period of 8 weeks in overweight and obese older adults (n=22) using a GC/MS metabolomic approach. After the 8 weeks, there were significant reductions in weight (7%) and metabolic improvement (glucose and lipid profile). Metabolomic analysis found that total saturated fatty acids (SFAs), including palmitic acid (C16:0) and stearic acid (C18:0) and monounsaturated fatty acids (MUFAs) were significantly decreased after the 8 week intervention.Furthermore, palmitoleic acid (C16:1) was found to be a negative predictor of change in body fat loss. Both the total ω-6 and ω-3 polyunsaturated fatty acids (PUFAs) significantly decreased although the overall total amounts of PUFAs did not. The branched chain amino acid (BCAA) isoleucine significantly decreased in the serum samples after the intervention. In conclusion, this study demonstrated that the weight loss intervention based on a hypocaloric diet identified changes in the metabolic profiles of serum in overweight and obese older adults, with a reduction in anthropometric and biochemical parameters also found.

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“…A number of direct and indirect links between FOXO, SP1 and IGFBP1 have already been uncovered. These results reveal a complex mechanism axis, which have been involved in the regulation of other gene expressions, biological functions and tumor growth [62-64]. As common ubiquitous transcription factor that binds to GC-rich motifs of several gene promoters, SP1 was involved in many cellular functions, such as growth, differentiation, and progression through regulation of several relevant genes [65].…”

Section: Discussionmentioning

confidence: 99%

Combination of Solamargine and Metformin Strengthens IGFBP1 Gene Expression Through Inactivation of Stat3 and Reciprocal Interaction Between FOXO3a and SP1

Tang

Zheng

et al. 2017

Cell Physiol Biochem

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Background/Aims: Solamargine, one natural photochemical component from traditional plants, has been shown to have anti-cancers properties. We previously showed that solamargine inhibited the growth of non-small-cell lung cancer (NSCLC) cells through suppression of prostaglandin E2 (PGE₂) receptor EP4 gene and regulation of downstream signaling pathways. However, the detailed mechanism underlying this, especially in combination of metformin, a known AMPK activator, still remained to be determined. Methods: Cell viability was measured using a 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and colorimetric 5-bromo-2-deoxyuridine (BrdU) ELISA methods, respectively. Western blot analysis and immunohistochemistry were performed to examine the phosphorylation and protein expressions of signal transducer and activator of transcription 3 (Stat3), SP1, forkhead box O3a (FOXO3a), and insulin-like growth factor (IGF)-IGF binding protein 1 (IGFBP1). The expression of IGFBP1 mRNA was measured by quantitative real time PCR (qRT-PCR). Silencing of FOXO3a and IGFBP1 were examined by siRNA procedures. Exogenously expression of SP1, FOXO3a, and IGFBP1 were carried out by transient transfection assays. The promoter activity of IGFBP1 was tested using Secrete-Pair^TM Dual Luminescence Assay Kit. A xenografted tumor model was used to further test the effect of solamargine in combining with metformin in vivo. Results: We further demonstrated that solamargine inhibited growth and induced cell cycle arrest in other NSCLC cell lines. Through mechanism-based approaches, we showed that solamargine decreased the phosphorylation of Stat3; In addition, solamargine induced FOXO3a, whereas reduced SP1 protein levels; all of which were abrogated in cells with overexpressed Stat3 gene. Interestingly, there is interaction between FOXO3a and SP1. Moreover, solamargine increased mRNA, protein expression and promoter activity of IGFBP1, which was not observed in cells with overexpressed SP1 or with silenced FOXO3a genes. Finally, ablation of IGFBP1 expression by siRNA blocked the effect of solamargine on cell growth inhibition. More importantly, there was a synergy of combination of solamargine and metformin. Similar findings were also observed in vivo. Conclusion: Our results show that solamargine increases IGFBP1 gene expression through inactivation of Stat3, followed by regulation and reciprocal interaction of FOXO3a and SP1 in vitro and in vivo. This ultimately leads to suppression of human lung cancer cell growth. Moreover, this is a synergy of solamargine in combination with metformin in this process. This study unravels a novel mechanism underlying the anti-lung cancer effects of solamargine in combination of metformin, and suggests a potential new lung cancer associated therapy.

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Docosahexaenoic acid suppresses the expression of FoxO and its target genes

Cited by 45 publications

References 57 publications

Tissue fatty acid deposition, plasma lipid and cytokine profile in pigs fed a diet with fish oil or palm oil

Tissue fatty acid deposition, plasma lipid and cytokine profile in pigs fed a diet with fish oil or palm oil

Metabolomics identifies changes in fatty acid and amino acid profiles in serum of overweight older adults following a weight loss intervention

Combination of Solamargine and Metformin Strengthens IGFBP1 Gene Expression Through Inactivation of Stat3 and Reciprocal Interaction Between FOXO3a and SP1

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