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The inverse association between ANGPTL8 and PI3KmTOR- PPARγ expressions in adipose tissue of highfructose- fed rats: The modulatory effect of kefir

Year 2021, Volume: 51 Issue: 3, 299 - 306, 29.12.2021

Fatma Akar , Ceren Güney , Hamdi Barbaros Özer , Mehmet Bilgehan Pektaş , Halit Buğra Koca , Aytac Kocabas , Gökhan Sadi

https://doi.org/10.26650/IstanbulJPharm.2021.933139

Abstract

Background and Aims: The dietary high-fructose intake might be a risk factor for several metabolic diseases. Kefir, a fermented milk product, has been proposed to have beneficial health effects. In this study, we aimed to investigate the effects of fructose consumption and kefir supplementation on the lipogenesis-related genes including angiopoietin-like protein 8 (angptl8), phosphoinositide 3-kinase (pi3k), mammalian target of rapamycin (mtor), and peroxisome proliferator-activated receptor γ (pparγ) as well as inflammatory factors in the adipose tissue to provide new mechanistic insights into lipogenesis. Methods: Fructose was given to the rats as a 20% solution in drinking water for 15 weeks. Kefir was administered by gastric gavage once a day during the final six weeks. Results: There was an upregulation of angptl8 mRNA expression in adipose tissue of rats given fructose. However, expressions of pi3k, mtor, and pparγ mRNAs were impaired in the adipose tissue. The increased interleukin (IL)-1β levels, but decreased IL-10, were also measured. There was no change in expressions of sirtuin1 (sirt1) and nuclear factor erythroid 2-related factor 2 (nrf2). Kefir supplementation suppressed expression of angptl8, but increased pi3k and mtor in the adipose tissue of high-fructose-fed rats. Conclusion: Activation of gene expression of angptl8, together with the suppression of pi3k, mtor, and pparγ, showed that there was an inverse association between these lipogenic genes in the adipose tissue of rats fed with high-fructose. Kefir supplementation has modulatory effects on fructose-induced changes except for pparγ expression. These findings showed that dietary fructose and kefir might reciprocally affect the lipogenesis-related genes in the adipose tissue.

Keywords

Dietary fructose Kefir ANGPTL8 PI3K-mTOR-PPARγ pathway Lipogenesis

Supporting Institution

Gazi University Research Fund

Project Number

BAP 02/2018-14

References

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Year 2021, Volume: 51 Issue: 3, 299 - 306, 29.12.2021

Fatma Akar , Ceren Güney , Hamdi Barbaros Özer , Mehmet Bilgehan Pektaş , Halit Buğra Koca , Aytac Kocabas , Gökhan Sadi

https://doi.org/10.26650/IstanbulJPharm.2021.933139

Abstract

Project Number

BAP 02/2018-14

References

  • Abu-Farha, M., Abubaker, J., Al-Khairi, I., Cherian, P., Noronha, F., Kavalakatt, S., ... Elkum, N. (2016). Circulating angiopoietin-like protein 8 (betatrophin) association with HsCRP and metabolic syndrome. Cardiovascular Diabetology, 15(1), 25.
  • Abu-Farha, M., Abubaker, J., Al-Khairi, I., Cherian, P., Noronha, F., Hu, F. B., ... Elkum, N. (2015). Higher plasma betatrophin/ANGPTL8 level in Type 2 Diabetes subjects does not correlate with blood glucose or insulin resistance. Scientific reports, 5(1), 1-8.
  • Akar, F., Uludağ, O., Aydın, A., Aytekin, Y. A., Elbeg, S., Tuzcu, M., & Sahin, K. (2012). High-fructose corn syrup causes vascular dysfunction associated with metabolic disturbance in rats: protective effect of resveratrol. Food and chemical toxicology, 50(6), 2135-2141.
  • Akar, F., Sumlu, E., Alçığır, M. E., Bostancı, A., & Sadi, G. (2021). Potential mechanistic pathways underlying intestinal and hepatic effects of kefir in high-fructose-fed rats. Food Research International, 143, 110287. https://doi.org/10.1016/j.foodres.2021.110287
  • Barroso, E., Rodríguez-Rodríguez, R., Chacón, M. R., Maymó-Masip, E., Ferrer, L., Salvadó, L., ... Vázquez-Carrera, M. (2015). PPARβ/δ ameliorates fructose-induced insulin resistance in adipocytes by preventing Nrf2 activation. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 1852(5), 1049-1058.
  • Bastard, J. P., Maachi, M., Lagathu, C., Kim, M. J., Caron, M., Vidal, H., ... Feve, B. (2006). Recent advances in the relationship between obesity, inflammation, and insulin resistance. European cytokine network, 17(1), 4-12.
  • Brown, M. S., & Goldstein, J. L. (2008). Selective versus total insulin resistance: a pathogenic paradox. Cell metabolism, 7(2), 95-96.
  • Carbone, C., Piro, G., Merz, V., Simionato, F., Santoro, R., Zecchetto, C., Tortora, G., & Melisi, D. (2018). Angiopoietin-Like Proteins in Angiogenesis, Inflammation and Cancer. International journal of molecular sciences, 19(2), 431.
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  • Chen, H. L., Tsai, T. C., Tsai, Y. C., Liao, J. W., Yen, C. C., & Chen, C. M. (2016). Kefir peptides prevent high-fructose corn syrup-induced non-alcoholic fatty liver disease in a murine model by modulation of inflammation and the JAK2 signaling pathway. Nutrition & diabetes, 6(12), e237-e237.
  • Choi, J. W., Kang, H. W., Lim, W. C., Kim, M. K., Lee, I. Y., & Cho, H. Y. (2017). Kefir prevented excess fat accumulation in diet-induced obese mice. Bioscience, biotechnology, and biochemistry, 81(5), 958-965.
  • Fu, Z., Berhane, F., Fite, A., Seyoum, B., Abou-Samra, A. B., & Zhang, R. (2014). Elevated circulating lipasin/betatrophin in human type 2 diabetes and obesity. Scientific reports, 4(1), 1-5.
  • Gao, J., Ding, G., Li, Q., Gong, L., Huang, J., & Sang, Y. (2019). Tibet kefir milk decreases fat deposition by regulating the gut microbiota and gene expression of Lpl and Angptl4 in high fat diet-fed rats. Food Research International, 121, 278-287.
  • García-Monzón, C., Petrov, P. D., Rey, E., Marañón, P., del Pozo-Maroto, E., Guzmán, C., ... Miquilena-Colina, M. E. (2018). Angiopoietin-like protein 8 is a novel vitamin d receptor target gene involved in nonalcoholic fatty liver pathogenesis. The American journal of pathology, 188(12), 2800-2810.
  • Han, C., Wei, S., He, F., Liu, D., Wan, H., Liu, H., ... Xu, F. (2015). The regulation of lipid deposition by insulin in goose liver cells is mediated by the PI3K-AKT-mTOR signaling pathway. PloS one, 10(5), e0098759.
  • Hannou, S. A., Haslam, D. E., McKeown, N. M., & Herman, M. A. (2018). Fructose metabolism and metabolic disease. The Journal of clinical investigation, 128(2), 545-555.
  • He, W., Barak, Y., Hevener, A., Olson, P., Liao, D., Le, J., ... Evans, R. M. (2003). Adipose-specific peroxisome proliferator-activated receptor γ knockout causes insulin resistance in fat and liver but not in muscle. Proceedings of the National Academy of Sciences, 100(26), 15712-15717.
  • Hu, H., Sun, W., Yu, S., Hong, X., Qian, W., Tang, B., ... Zhou, L. (2014). Increased circulating levels of betatrophin in newly diagnosed type 2 diabetic patients. Diabetes care, 37(10), 2718-2722.
  • Huang, X., Liu, G., Guo, J., & Su, Z. (2018). The PI3K/AKT pathway in obesity and type 2 diabetes. International journal of biological sciences, 14(11), 1483.
  • Izumi, R., Kusakabe, T., Noguchi, M., Iwakura, H., Tanaka, T., Miyazawa, T., ... Nakao, K. (2018). CRISPR/Cas9-mediated Angptl8 knockout suppresses plasma triglyceride concentrations and adiposity in rats. Journal of lipid research, 59(9), 1575-1585.
  • Janssen, A. W., Katiraei, S., Bartosinska, B., Eberhard, D., van Dijk, K. W., & Kersten, S. (2018). Loss of angiopoietin-like 4 (ANGPTL4) in mice with diet-induced obesity uncouples visceral obesity from glucose intolerance partly via the gut microbiota. Diabetologia, 61(6), 1447-1458.
  • Jensen, T., Abdelmalek, M. F., Sullivan, S., Nadeau, K. J., Green, M., Roncal, C., ... Tolan, D. R. (2018). Fructose and sugar: A major mediator of non-alcoholic fatty liver disease. Journal of hepatology, 68(5), 1063-1075.
  • Kim, D. H., Jeong, D., Kim, H., & Seo, K. H. (2019). Modern perspectives on the health benefits of kefir in next generation sequencing era: Improvement of the host gut microbiota. Critical reviews in food science and nutrition, 59(11), 1782-1793.
  • Korkmaz, O. A., Sumlu, E., Koca, H. B., Pektas, M. B., Kocabas, A., Sadi, G., & Akar, F. (2019a). Effects of Lactobacillus plantarum and Lactobacillus helveticus on renal insulin signaling, inflammatory markers, and glucose transporters in high-fructose-fed rats. Medicina, 55(5), 207.
  • Korkmaz, O. A., Sadi, G., Kocabaş, A., Yıldırım, O. G., Sumlu, E., Koca, H. B., … Akar F. (2019b). Lactobacillus helveticus and Lactobacillus plantarum modulate renal antioxidant status in a rat model of fructose-induced metabolic syndrome. Archives of Biological Sciences, 71 (2), 265-273.
  • Laplante, M., & Sabatini, D. M. (2012). mTOR signaling in growth control and disease. Cell, 149(2), 274-293.
  • Lee, Y. H., Lee, S. G., Lee, C. J., Kim, S. H., Song, Y. M., Yoon, M. R., ... Lee, H. C. (2016). Association between betatrophin/ANGPTL8 and non-alcoholic fatty liver disease: animal and human studies. Scientific reports, 6(1), 1-12.
  • Li, H., Yu, L., & Zhao, C. (2019). Dioscin attenuates high fat diet induced insulin resistance of adipose tissue through the IRS 1/PI3K/Akt signaling pathway. Molecular medicine reports, 19(2), 1230-1237.
  • Li, S., Brown, M. S., & Goldstein, J. L. (2010). Bifurcation of insulin signaling pathway in rat liver: mTORC1 required for stimulation of lipogenesis, but not inhibition of gluconeogenesis. Proceedings of the national academy of sciences, 107(8), 3441-3446.
  • Ma, X., Lin, L., Yue, J., Pradhan, G., Qin, G., Minze, L. J., ... Sun, Y. (2013). Ghrelin receptor regulates HFCS-induced adipose inflammation and insulin resistance. Nutrition & diabetes, 3(12), e99-e99.
  • Nakamura, F., Ishida, Y., Sawada, D., Ashida, N., Sugawara, T., Sakai, M., ... Fujiwara, S. (2016). Fragmented lactic Acid bacterial cells activate peroxisome proliferator-activated receptors and ameliorate Dyslipidemia in obese mice. Journal of agricultural and food chemistry, 64(12), 2549-2559.
  • Nidhina Haridas, P. A., Soronen, J., Sädevirta, S., Mysore, R., Quagliarini, F., Pasternack, A., ... Fischer-Posovszky, P. (2015). Regulation of angiopoietin-like proteins (ANGPTLs) 3 and 8 by insulin. The Journal of Clinical Endocrinology & Metabolism, 100(10), E1299-E1307.
  • Okada, T., Kawano, Y., Sakakibara, T., Hazeki, O., & Ui, M. (1994). Essential role of phosphatidylinositol 3-kinase in insulin-induced glucose transport and antilipolysis in rat adipocytes. Studies with a selective inhibitor wortmannin. Journal of Biological Chemistry, 269(5), 3568-3573.
  • Oldoni, F., Cheng, H., Banfi, S., Gusarova, V., Cohen, J. C., & Hobbs, H. H. (2020). ANGPTL8 has both endocrine and autocrine effects on substrate utilization. JCI insight, 5(17).
  • Pektas, M. B., Sadi, G., & Akar, F. (2015). Long-term dietary fructose causes gender-different metabolic and vascular dysfunction in rats: modulatory effects of resveratrol. Cellular physiology and biochemistry, 37(4), 1407-1420.
  • Pektas, M. B., Koca, H. B., Sadi, G., & Akar, F. (2016). Dietary fructose activates insulin signaling and inflammation in adipose tissue: Modulatory role of resveratrol. BioMed Research International, 2016(8014252), 1–10.
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There are 56 citations in total.

Details

Primary Language English
Subjects Pharmacology and Pharmaceutical Sciences
Journal Section Original Article
Authors

Fatma Akar 0000-0002-5432-0304

Ceren Güney 0000-0002-3267-2886

Hamdi Barbaros Özer 0000-0001-6669-0444

Mehmet Bilgehan Pektaş 0000-0003-0055-7688

Halit Buğra Koca 0000-0002-5353-3228

Aytac Kocabas 0000-0001-7622-1932

Gökhan Sadi 0000-0002-6422-1203

Project Number BAP 02/2018-14
Publication Date December 29, 2021
Submission Date May 5, 2021
Published in Issue Year 2021 Volume: 51 Issue: 3

Cite

APA Akar, F., Güney, C., Özer, H. B., Pektaş, M. B., et al. (2021). The inverse association between ANGPTL8 and PI3KmTOR- PPARγ expressions in adipose tissue of highfructose- fed rats: The modulatory effect of kefir. İstanbul Journal of Pharmacy, 51(3), 299-306. https://doi.org/10.26650/IstanbulJPharm.2021.933139
AMA Akar F, Güney C, Özer HB, Pektaş MB, Koca HB, Kocabas A, Sadi G. The inverse association between ANGPTL8 and PI3KmTOR- PPARγ expressions in adipose tissue of highfructose- fed rats: The modulatory effect of kefir. iujp. December 2021;51(3):299-306. doi:10.26650/IstanbulJPharm.2021.933139
Chicago Akar, Fatma, Ceren Güney, Hamdi Barbaros Özer, Mehmet Bilgehan Pektaş, Halit Buğra Koca, Aytac Kocabas, and Gökhan Sadi. “The Inverse Association Between ANGPTL8 and PI3KmTOR- PPARγ Expressions in Adipose Tissue of Highfructose- Fed Rats: The Modulatory Effect of Kefir”. İstanbul Journal of Pharmacy 51, no. 3 (December 2021): 299-306. https://doi.org/10.26650/IstanbulJPharm.2021.933139.
EndNote Akar F, Güney C, Özer HB, Pektaş MB, Koca HB, Kocabas A, Sadi G (December 1, 2021) The inverse association between ANGPTL8 and PI3KmTOR- PPARγ expressions in adipose tissue of highfructose- fed rats: The modulatory effect of kefir. İstanbul Journal of Pharmacy 51 3 299–306.
IEEE F. Akar, C. Güney, H. B. Özer, M. B. Pektaş, H. B. Koca, A. Kocabas, and G. Sadi, “The inverse association between ANGPTL8 and PI3KmTOR- PPARγ expressions in adipose tissue of highfructose- fed rats: The modulatory effect of kefir”, iujp, vol. 51, no. 3, pp. 299–306, 2021, doi: 10.26650/IstanbulJPharm.2021.933139.
ISNAD Akar, Fatma et al. “The Inverse Association Between ANGPTL8 and PI3KmTOR- PPARγ Expressions in Adipose Tissue of Highfructose- Fed Rats: The Modulatory Effect of Kefir”. İstanbul Journal of Pharmacy 51/3 (December 2021), 299-306. https://doi.org/10.26650/IstanbulJPharm.2021.933139.
JAMA Akar F, Güney C, Özer HB, Pektaş MB, Koca HB, Kocabas A, Sadi G. The inverse association between ANGPTL8 and PI3KmTOR- PPARγ expressions in adipose tissue of highfructose- fed rats: The modulatory effect of kefir. iujp. 2021;51:299–306.
MLA Akar, Fatma et al. “The Inverse Association Between ANGPTL8 and PI3KmTOR- PPARγ Expressions in Adipose Tissue of Highfructose- Fed Rats: The Modulatory Effect of Kefir”. İstanbul Journal of Pharmacy, vol. 51, no. 3, 2021, pp. 299-06, doi:10.26650/IstanbulJPharm.2021.933139.
Vancouver Akar F, Güney C, Özer HB, Pektaş MB, Koca HB, Kocabas A, Sadi G. The inverse association between ANGPTL8 and PI3KmTOR- PPARγ expressions in adipose tissue of highfructose- fed rats: The modulatory effect of kefir. iujp. 2021;51(3):299-306.
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