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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

Yıl 2021, Cilt: 51 Sayı: 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

Öz

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.

Anahtar Kelimeler

Dietary fructose Kefir ANGPTL8 PI3K-mTOR-PPARγ pathway Lipogenesis

Destekleyen Kurum

Gazi University Research Fund

Proje Numarası

BAP 02/2018-14

Kaynakça

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  • 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.
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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.
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  • 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.
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  • 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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Yıl 2021, Cilt: 51 Sayı: 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

Öz

Proje Numarası

BAP 02/2018-14

Kaynakça

  • 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.
  • Chen, C. C., Susanto, H., Chuang, W. H., Liu, T. Y., & Wang, C. H. (2016). Higher serum betatrophin level in type 2 diabetes subjects is associated with urinary albumin excretion and renal function. Cardiovascular diabetology, 15(1), 1-9.
  • 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.
  • Quagliarini, F., Wang, Y., Kozlitina, J., Grishin, N. V., Hyde, R., Boerwinkle, E., ... Hobbs, H. H. (2012). Atypical angiopoietin-like protein that regulates ANGPTL3. Proceedings of the National Academy of Sciences, 109(48), 19751-19756.
  • Ren, G., Kim, J. Y., & Smas, C. M. (2012). Identification of RIFL, a novel adipocyte-enriched insulin target gene with a role in lipid metabolism. American Journal of Physiology-Endocrinology and Metabolism, 303(3), E334-E351.
  • Rondinone, C. M., Wang, L. M., Lonnroth, P., Wesslau, C., Pierce, J. H., & Smith, U. (1997). Insulin receptor substrate (IRS) 1 is reduced and IRS-2 is the main docking protein for phosphatidylinositol 3-kinase in adipocytes from subjects with non-insulin-dependent diabetes mellitus. Proceedings of the National Academy of Sciences, 94(8), 4171-4175.
  • Rosa, D. D., Dias, M. M., Grześkowiak, Ł. M., Reis, S. A., Conceição, L. L., & Maria do Carmo, G. P. (2017). Milk kefir: nutritional, microbiological and health benefits. Nutrition research reviews, 30(1), 82-96.
  • Rosa, D. D., Grześkowiak, Ł. M., Ferreira, C. L., Fonseca, A. C. M., Reis, S. A., Dias, M. M., ... Machado, A. B. (2016). Kefir reduces insulin resistance and inflammatory cytokine expression in an animal model of metabolic syndrome. Food & function, 7(8), 3390-3401.
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  • Shan, T., Zhang, P., Jiang, Q., Xiong, Y., Wang, Y., & Kuang, S. (2016). Adipocyte-specific deletion of mTOR inhibits adipose tissue development and causes insulin resistance in mice. Diabetologia, 59(9), 1995-2004.
  • Sumlu, E., Bostancı, A., Sadi, G., Alçığır, M. E., & Akar, F. (2020). Lactobacillus plantarum improves lipogenesis and IRS-1/AKT/eNOS signalling pathway in the liver of high-fructose-fed rats. Archives of Physiology and Biochemistry, 1-9.
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  • Wang, H., Lai, Y., Han, C., Liu, A., Fan, C., Wang, H., ... Shan, Z. (2016). The effects of serum ANGPTL8/betatrophin on the risk of developing the metabolic syndrome–a prospective study. Scientific reports, 6(1), 1-8.
  • Wang, Y., Quagliarini, F., Gusarova, V., Gromada, J., Valenzuela, D. M., Cohen, J. C., & Hobbs, H. H. (2013). Mice lacking ANGPTL8 (Betatrophin) manifest disrupted triglyceride metabolism without impaired glucose homeostasis. Proceedings of the National Academy of Sciences, 110(40), 16109-16114.
  • Yamauchi, T., Kamon, J., Waki, H., Murakami, K., Motojima, K., Komeda, K., ... Kadowaki, T. (2001). The mechanisms by which both heterozygous peroxisome proliferator-activated receptor γ (PPARγ) deficiency and PPARγ agonist improve insulin resistance. Journal of Biological Chemistry, 276(44), 41245-41254.
  • Yildirim, O. G., Sumlu, E., Aslan, E., Koca, H. B., Pektas, M. B., Sadi, G., & Akar, F. (2019). High-fructose in drinking water initiates activation of inflammatory cytokines and testicular degeneration in rat. Toxicology mechanisms and methods, 29(3), 224-232.
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Toplam 56 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Eczacılık ve İlaç Bilimleri
Bölüm Original Article
Yazarlar

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

Proje Numarası BAP 02/2018-14
Yayımlanma Tarihi 29 Aralık 2021
Gönderilme Tarihi 5 Mayıs 2021
Yayımlandığı Sayı Yıl 2021 Cilt: 51 Sayı: 3

Kaynak Göster

APA Akar, F., Güney, C., Özer, H. B., Pektaş, M. B., vd. (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. Aralık 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, ve 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, sy. 3 (Aralık 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 (01 Aralık 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, ve G. Sadi, “The inverse association between ANGPTL8 and PI3KmTOR- PPARγ expressions in adipose tissue of highfructose- fed rats: The modulatory effect of kefir”, iujp, c. 51, sy. 3, ss. 299–306, 2021, doi: 10.26650/IstanbulJPharm.2021.933139.
ISNAD Akar, Fatma vd. “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 (Aralık 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 vd. “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, c. 51, sy. 3, 2021, ss. 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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