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ORIGINAL ARTICLE
Kefir Prevents Adipose Tissue Growth Through the Induction of Apoptotic Elements in High-Fructose Corn Syrup-Fed Rats
 
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1
Department of Histology and Embryology, Faculty of Medicine, Afyonkarahisar Health Sciences University, 03200, Afyonkarahisar, Turkey
 
2
Department of Biology, K.Ö. Science Faculty, Karamanoglu Mehmetbey University, 70100, Karaman, Turkey
 
3
Department of Anatomy, Faculty of Medicine, Afyonkarahisar Health Sciences University, 03200, Afyonkarahisar, Turkey
 
4
Department of Chemistry, Faculty of Science, Yildiz Technical University, 34220, Istanbul, Turkey
 
5
Department of Obstetrics and Gynecology, Faculty of Medicine, Afyonkarahisar Health Sciences University, 03200, Afyonkarahisar, Turkey
 
6
Department of Pediatrics, Faculty of Medicine, Afyonkarahisar Health Sciences University, 03200, Afyonkarahisar, Turkey
 
7
Department of Medical Pharmacology, Faculty of Medicine, Afyonkarahisar Health Sciences University, 03200, Afyonkarahisar, Turkey
 
 
Submission date: 2023-01-07
 
 
Acceptance date: 2023-03-27
 
 
Online publication date: 2023-05-05
 
 
Publication date: 2023-05-05
 
 
Corresponding author
Mehmet Bilgehan Pektas   

Department of Medical Pharmacology, Faculty of Medicine, Afyonkarahisar Health Sciences University, 03200, Afyonkarahisar, Turkey
 
 
Pol. J. Food Nutr. Sci. 2023;73(2):120-129
 
KEYWORDS
TOPICS
ABSTRACT
Consumption of high-fructose corn syrup (HFCS) in the diet is a causal factor in the development of abdominal obesity; however, the molecular mechanism behind this association is still up for debate. This study evaluated the metabolic disturbances that are caused by HFCS on adipose tissue as well as the possibility of kefir as a therapy to prevent these metabolic disturbances. Male Wistar rats were divided into four groups: control, kefir, HFCS, and HFCS+kefir. HFCS (20%, w/v) was given in drinking water and kefir (1 mL/100 g body weight) by gastric gavage daily for 8 weeks. Levels of insulin signaling, inflammation, and apoptosis-associated proteins of adipose tissues were determined with Western blot and immunohistochemical techniques. Gene expressions were evaluated with semi-quantitative real-time polymerase chain reaction (qRT-PCR). The indirect terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) method was used to assess changes in apoptotic cells, and hematoxylin/eosin staining to determine adipocyte number and diameter. Accordingly, HFCS boosted protein kinase B (Akt) and p-Akt while reducing nuclear factor κB (NF-κB), and tumor necrosis factor alpha (TNFα) levels and kefir treatment restored Akt induction in HFCS-treated rats despite raising NF-κB, and TNFα. Increased expression of Akt and B-cell lymphoma-2 gene (Bcl2) was contrasted with decreased expression of Nfkb, Tnfa, tumor protein 53 gene (p53), and caspase-8 gene (Casp8). Furthermore, while there was a marked reduction in TUNEL-positive cells in the HFCS group, the number of such cells was greater in the HFCS+kefir group. These results show that HFCS intake suppresses apoptosis in adipose tissues, which may be responsible for tissue development and abdominal obesity and may be reversed with kefir administration due to the activation of apoptosis-associated genes and proteins.
ACKNOWLEDGEMENTS
The authors would like to appreciate Danem-Kefir (Isparta, TURKEY) for providing kefir.
FUNDING
The study did not receive any external funding.
CONFLICT OF INTEREST
The authors of this manuscript report no conflict of interests. All co-authors have seen and agreed with the contents of the manuscript.
 
REFERENCES (51)
1.
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, art. no. 110287. https://doi.org/10.1016/j.food....
 
2.
Badr El-Din, N.K., Shabana, S.M., Abdulmajeed, B.A., Ghoneum, M. (2020). A novel kefir product (PFT) inhibits Ehrlich ascites carcinoma in mice via induction of apoptosis and immunomodulation. BMC Complementary Medicine and Therapies, 20(1), art. no. 127. https://doi.org/10.1186/s12906....
 
3.
Barros, S.É.L., Rocha, C.S., de Moura, M.S.B., Barcelos, M.P., da Silva, C.H.T.P., Hage-Melim, L.I.S. (2021). Potential beneficial effects of kefir and its postbiotic, kefiran, on child food allergy. Food and Function, 12(9), 3770–3786. https://doi.org/10.1039/D0FO03....
 
4.
Barzilay, J., Freedland, E. (2003). Inflammation and its association with glucose disorders and cardiovascular disease. Treatments in Endocrinology, 2(2), 85–94. https://doi.org/10.2165/000246....
 
5.
Berger, N.A. (2014). Obesity and cancer pathogenesis. Annals of the New York Academy of Sciences, 1311(1), 57–76. https://doi.org/10.1111/nyas.1....
 
6.
Bozkurt, E., Atay, E., Pektaş, G., Ertekin, A., Vurmaz, A., Korkmaz, Ö.A., Sadi, G., Aslan, E., Koca, O.H., Pektaş, M.B. (2020). Potential anti-tumor activity of kefir-induced juglone and resveratrol fractions against Ehrlich ascites carcinoma-bearing BALB/c mice. Iranian Journal of Pharmaceutical Research, 19(3), 358–369. https://doi.org/10.22037/ijpr.....
 
7.
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 and Diabetes, 6, art. no. e237. https://doi.org/10.1038/nutd.2....
 
8.
Choe, S.S., Huh, J.Y., Hwang, I.J., Kim, J.I., Kim, J.B. (2016). Adipose tissue remodeling: Its role in energy metabolism and metabolic disorders. Frontiers in Endocrinology (Lausanne), 7, art. no. 30. https://doi.org/10.3389/fendo.....
 
9.
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. https://doi.org/10.1080/091684....
 
10.
DiNunzio, G., Belew, G.D., Torres, A.N., Silva, J.G., Silva, L.P., Barosa, C., Tavares, L., Jones, J.G. (2020). Determining the contribution of a high-fructose corn syrup formulation to hepatic glycogen synthesis during ad-libitum feeding in mice. Scientific Reports, 10(1), art. no. 12852. https://doi.org/10.1038/s41598....
 
11.
Duncan, B.B., Schmidt, M.I., Pankow, J.S., Ballantyne, C.M., Couper, D., Vigo, A., Hoogeveen, R., Folsom, A.R., Heiss, G. (2003). Low-grade systemic inflammation and the development of type 2 diabetes: The atherosclerosis risk in communities study. Diabetes, 52(7), 1799–1805. https://doi.org/10.2337/diabet....
 
12.
Ekici, Ö., Aslan, E., Aladağ, T., Güzel, H., Korkmaz, Ö.A., Bostancı, A., Sadi, G., Pektaş, M.B. (2022a). Masseter muscle and gingival tissue inflammatory response following treatment with high-fructose corn syrup in rats: Anti-inflammatory and antioxidant effects of kefir. Journal of Food Biochemistry, 46(3), art. no. e13732. https://doi.org/10.1111/jfbc.1....
 
13.
Ekici, O., Aslan, E., Guzel, H., Korkmaz, O.A., Sadi, G., Gurol, A.M., Boyaci, M.G., Pektas, M.B. (2022b). Kefir alters craniomandibular bone development in rats fed excess dose of high fructose corn syrup. Journal of Bone and Mineral Metabolism, 40(1), 56–65. https://doi.org/10.1007/s00774....
 
14.
El Golli-Bennour, E., Timoumi, R., Koroit, M., Bacha, H., Abid-Essefi, S. (2019). Protective effects of kefir against zearalenone toxicity mediated by oxidative stress in cultured HCT-116 cells. Toxicon, 157, 25–34. https://doi.org/10.1016/j.toxi....
 
15.
Esener, O.B.B., Balkan, B.M., Armutak, E.I., Uvez, A., Yildiz, G., Hafizoglu, M., Yilmazer, N., Gurel-Gurevin, E. (2018). Donkey milk kefir induces apoptosis and suppresses proliferation of Ehrlich ascites carcinoma by decreasing iNOS in mice. Biotechnic and Histochemistry, 93(6), 424–431. https://doi.org/10.1080/105202....
 
16.
Furuno, T., Nakanishi, M. (2012). Kefiran suppresses antigen-induced mast cell activation. Biological and Pharmaceutical Bulletin, 35(2), 178–183. https://doi.org/10.1248/bpb.35....
 
17.
Hamida, R.S., Shami, A., Ali, M.A., Almohawes, Z.N., Mohammed, A.E., Bin-Meferij, M.M. (2021). Kefir: A protective dietary supplementation against viral infection. Biomedicine and Pharmacotherapy, 133, art. no. 110974. https://doi.org/10.1016/j.biop....
 
18.
Harvey, A.E., Lashinger, L.M., Hursting, S.D. (2011). The growing challenge of obesity and cancer: an inflammatory issue. Annals of the New York Academy of Sciences, 1229(1), 45–52. https://doi.org/10.1111/j.1749....
 
19.
Hattori, H., Hanai, Y., Oshima, Y., Kataoka, H., Eto, N. (2021). Excessive intake of high-fructose corn syrup drinks induces impaired glucose tolerance. Biomedicines, 9(5), art. no. 541. https://doi.org/10.3390/biomed....
 
20.
Hill, D., Conner, M., Clancy, F., Moss, R., Wilding, S., Bristow, M., O'Connor, D.B. (2022). Stress and eating behaviours in healthy adults: a systematic review and meta-analysis. Health Psychology Review, 16(2), 280–304. https://doi.org/10.1080/174371....
 
21.
Irigaray, P., Newby, J.A., Lacomme, S., Belpomme, D. (2007). Overweight/obesity and cancer genesis: More than a biological link. Biomedicine and Pharmacotherapy, 61(10), 665–678. https://doi.org/10.1016/j.biop....
 
22.
Khorshidian, N., Shadnoush, M., Zabihzadeh Khajavi, M., Sohrabvandi, S., Yousefi, M., Mortazavian, A.M. (2021). Fructose and high fructose corn syrup: are they a two-edged sword? International Journal of Food Sciences and Nutrition, 72(5), 592–614. https://doi.org/10.1080/096374....
 
23.
Korkmaz, O.A., Sumlu, E., Koca, H.B., Pektas, M.B., Kocabas, A., Sadi, G., Akar, F. (2019). Effects of Lactobacillus plantarum and Lactobacillus helveticus on renal insulin signaling, inflammatory markers, and glucose transporters in high-fructose-fed rats. Medicina, 55(5), art. no. 207. https://doi.org/10.3390/medici....
 
24.
Lee, W.-C., Leu, S., Wu, K.L.H., Tain, Y.-L., Chuang, Y.-C., Chan, J.Y.H. (2021). Tadalafil ameliorates bladder overactivity by restoring insulin-activated detrusor relaxation via the bladder mucosal IRS/PI3K/AKT/eNOS pathway in fructose-fed rats. Scientific Reports, 11(1), art. no. 8202. https://doi.org/10.1038/s41598....
 
25.
Li, K.-P., Yu, Y., Yuan, M., Zhang, C.-M., Rong, X.-L., Turnbull, J.E., Guo, J. (2021). Tian-Huang formula, a traditional Chinese medicinal prescription, improves hepatosteatosis and glucose intolerance targeting AKT-SREBP nexus in diet-induced obese rats. Evidence-Based Complementary and Alternative Medicine, 2021, art. no. 6617586. https://doi.org/10.1155/2021/6....
 
26.
Liu, Y., Wang, C., Wei, M., Yang, G., Yuan, L. (2021). Multifaceted roles of adipose tissue-derived exosomes in physiological and pathological conditions. Frontiers in Physiology, 12, art. no. 669429. https://doi.org/10.3389/fphys.....
 
27.
Lowry, O.H., Rosebrough, N.J., Farr, A.L., Randall, R.J. (1951). Protein measurement with the Folin phenol reagent. Journal of Biological Chemistry, 193(1), 265–275. https://doi.org/10.1016/S0021-....
 
28.
Maines, E., Franceschi, R., Martinelli, D., Soli, F., Lepri, F.R., Piccoli, G., Soffiati, M. (2021). Hypoglycemia due to PI3K/AKT/mTOR signaling pathway defects: two novel cases and review of the literature. Hormones, 20(4), 623–640. https://doi.org/10.1007/s42000....
 
29.
Markowiak, P., Śliżewska, K. (2017). Effects of probiotics, prebiotics, and synbiotics on human health. Nutrients, 9(9), art. no. 1021. https://doi.org/10.3390/nu9091....
 
30.
National Health and Medical Research Council (2013). Australian Code for the Care and Use of Animals for Scientific Purposes. 8th edition. National Health and Medical Research Council, Canberra, Australia. Available from: http://www.nhmrc.gov.au/guidel....
 
31.
National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals (2011). Guide for the Care and Use of Laboratory Animals. 8th edition. National Academies Press (US), Washington, DC, USA. Available from: https://www.ncbi.nlm.nih.gov/b.... https://doi.org/10.17226/12910.
 
32.
Narayanankutty, A., Kuzhivelil, B.T., Raghavamenon, A.C. (2022). A high-fructose diet formulated with thermally oxidized monounsaturated fat aggravates metabolic dysregulation in colon epithelial tissues of rats. Journal of the American Nutrition Association, 41(1), 38–49. https://doi.org/10.1080/073157....
 
33.
Nephan, G., Coskun, Z.M., Bolkent, S. (2018). Dipeptidyl peptidase-4 inhibition prevents cell death via extrinsic and intrinsic apoptotic pathways in rat pancreas with insulin resistance. Cell Biochemistry and Function, 36(4), 212–220. https://doi.org/10.1002/cbf.33....
 
34.
Pektaş, M.B., Aslan, E., Güzel, H., Korkmaz, Ö.A., Çeleğen, K, Pektaş, A., Bostanci, A., Sadi, G. (2022). Kefir protects the liver against high fructose corn syrup induced phosphodiesterase hyperactivity. Turkish Journal of Biochemistry, 47(3), 351–360. https://doi.org/10.1515/tjb-20....
 
35.
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, art. no. 8014252. https://doi.org/10.1155/2016/8....
 
36.
Prasatthong, P., Meephat, S., Rattanakanokchai, S., Bunbupha, S., Prachaney, P., Maneesai, P., Pakdeechote, P. (2021). Hesperidin ameliorates signs of the metabolic syndrome and cardiac dysfunction via IRS/Akt/GLUT4 signaling pathway in a rat model of diet-induced metabolic syndrome. European Journal of Nutrition, 60(2), 833–848. https://doi.org/10.1007/s00394....
 
37.
Qiao, Y., Xu, L., Tao, X., Yin, L., Qi, Y., Xu, Y., Han, X., Tang, Z., Ma, X., Liu, K., Peng, J. (2018). Protective effects of dioscin against fructose-induced renal damage via adjusting Sirt3-mediated oxidative stress, fibrosis, lipid metabolism and inflammation. Toxicology Letters, 284, 37–45. https://doi.org/10.1016/j.toxl....
 
38.
Rosa, D.D., Grześkowiak, Ł.M., Ferreira, C.L.L.F., Fonseca, A.C.M., Reis, S.A., Dias, M.M., Siqueira, N.P., Silva, L.L., Neves, C.A., Oliveira, L.L., Machado, A.B.F., Peluzio, M.C.P. (2016). Kefir reduces insulin resistance and inflammatory cytokine expression in an animal model of metabolic syndrome. Food and Function, 7(8), 3390–3401. https://doi.org/10.1039/C6FO00....
 
39.
Sadowska, J., Rygielska, M. (2019). The effect of high fructose corn syrup on the plasma insulin and leptin concentration, body weight gain and fat accumulation in rat. Advances in Clinical and Experimental Medicine, 28(7), 879–884. https://doi.org/10.17219/acem/....
 
40.
Savran, M., Asci, H., Ozmen, O., Erzurumlu, Y., Savas, H.B., Sonmez, Y., Sahin, Y. (2019). Melatonin protects the heart and endothelium against high fructose corn syrup consumption-induced cardiovascular toxicity via SIRT-1 signaling. Human and Experimental Toxicology, 38(10), 1212–1223. https://doi.org/10.1177/096032....
 
41.
Sohn, J.H., Lee, Y.K., Han, J.S., Jeon, Y.G., Kim, J.I., Choe, S.S., Kim, S.J., Yoo, H.J., Kim, J.B. (2018). Perilipin 1 (Plin1) deficiency promotes inflammatory responses in lean adipose tissue through lipid dysregulation. Journal of Biological Chemistry, 293(36), 13974–13988. https://doi.org/10.1074/jbc.RA....
 
42.
Stanhope, K.L. (2016). Sugar consumption, metabolic disease and obesity: The state of the controversy. Critical Reviews in Clinical Laboratory Sciences, 53(1), 52–67. https://doi.org/10.3109/104083....
 
43.
Stephens, J.M., Lee, J., Pilch, P.F. (1997). Tumor necrosis factor-α-induced insulin resistance in 3T3-L1 adipocytes is accompanied by a loss of insulin receptor substrate-1 and GLUT4 expression without a loss of insulin receptor-mediated signal transduction. Journal of Biological Chemistry, 272(2), 971–976. https://doi.org/10.1074/jbc.27....
 
44.
Stephens, J.M., Pekala, P.H. (1992). Transcriptional repression of the C/EBP-alpha and GLUT4 genes in 3T3-L1 adipocytes by tumor necrosis factor-alpha. Regulations is coordinate and independent of protein synthesis. Journal of Biological Chemistry, 267(19), 13580–13584. https://doi.org/10.1016/S0021-....
 
45.
Sumlu, E., Bostancı, A., Sadi, G., Alçığır, M.E., Akar, F. (2022). Lactobacillus plantarum improves lipogenesis and IRS-1/AKT/eNOS signalling pathway in the liver of high-fructose-fed rats. Archives of Physiology and Biochemistry, 128(3), 786–794. https://doi.org/10.1080/138134....
 
46.
Veličković, N., Djordjevic, A., Vasiljević, A., Bursać, B., Milutinović, D.V., Matić, G. (2013). Tissue-specific regulation of inflammation by macrophage migration inhibitory factor and glucocorticoids in fructose-fed Wistar rats. British Journal of Nutrition, 110(3), 456–465. https://doi.org/10.1017/S00071....
 
47.
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. https://doi.org/10.1080/153765....
 
48.
Zafar, M.I., Frese, M., Mills, K.E. (2021). Chronic fructose substitution for glucose or sucrose in food or beverages and metabolic outcomes: An updated systematic review and meta-analysis. Frontiers in Nutrition, 8, art. no. 647600. https://doi.org/10.3389/fnut.2....
 
49.
Zaki, S.M., Fattah, S.A., Hassan, D.S. (2019). The differential effects of high-fat and high-fructose diets on the liver of male albino rat and the proposed underlying mechanisms. Folia Morphologica, 78(1), 124–136. https://doi.org/10.5603/FM.a20....
 
50.
Zhang, H.-J., Chen, C., Ding, L., Shi, H.-H., Wang, C.-C., Xue, C.-H., Zhang, T.-T., Wang, Y.-M. (2020). Sea cucumbers-derived sterol sulfate alleviates insulin resistance and inflammation in high-fat-high-fructose diet-induced obese mice. Pharmacological Research, 160, art. no. 105191. https://doi.org/10.1016/j.phrs....
 
51.
Zubiría, M.G., Gambaro, S.E., Rey, M.A., Carasi, P., Serradell, M.Á., Giovambattista, A. (2017). Deleterious metabolic effects of high fructose intake: The preventive effect of Lactobacillus kefiri administration. Nutrients, 9(5), art. no. 470. https://doi.org/10.3390/nu9050....
 
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