Leptin, Mikrobiyota ve Obezite İlişkisi

Abstract

Obezite vücut yağ dengesinin bozulması ile karakterize olan küresel bir sağlık sorunudur. Bu sorunla mücadelede yeni bakış açıları kazanabilmek için obezite gelişimi ve ilerlemesi ile ilgili biyokimyasal, fizyolojik vb. süreçleri anlamaya yönelik çeşitli araştırmalar yapılmaktadır. Tokluk hormonu olarak adlandırılan leptin, iştah metabolizmasından bağışıklık sistemine birçok yaşamsal faaliyette görevli olmakla beraber enerji homeostazında da etkilidir. Vücut ağırlığının düzenlenmesinde büyük rol oynayan leptin hormonunun sinyalizasyonundaki ya da bileşenlerindeki genetik bozukluklar leptin direncine dolayısıyla da obeziteye neden olabilmektedir. Bunun yanı sıra bağırsak mikrobiyotasının da obezite, insülin direnci, gibi pek çok metabolik bozukluğunda patogenezinde olası katkıları araştırılmaktadır. Bağırsak mikrobiyotası; besin sindirimi ve emilimi, çeşitli iştah hormonları veya peptitlerinin salgılanmasının düzenlenmesi gibi birçok metabolik olaydan sorumludur ve mikrobiyotadaki bozukluklar da obezite için risk faktörüdür. Ayrıca bağırsak mikrobiyotasının leptin ile bağlantılı olduğu bunun da obezite üzerinde etkili olabileceği yapılan çalışmalarla desteklenmektedir. Bu derleme obezitenin etiyolojisinde mikrobiyota ve leptin hormonunun rolüne dikkat çekebilmek amacıyla araştırılan güncel bilgiler doğrultusunda hazırlanmıştır. Araştırma hakemli dergilerde yayınlanan ve PubMed, Web of Science ve Google Scholar’da taranan yayınlardan derlenmiştir. Bu amaçla leptin, bağırsak mikrobiyotası, obezite, leptin direnci anahtar kelimeleri birlikte kullanılmış ve bu çalışmada araştırma makalelerine yer verilmiştir.

Keywords

• Leptin
• bağırsak mikrobiyotası
• obezite
• leptin direnci
• mikroorganizma

The Relationship of Leptin, Microbiota and Obesity

Abstract

Obesity is a global health problem characterized by the deterioration of body fat balance. In order to gain new perspectives in the contend with this problem, various researches are carried out to understand the biochemical, physiological, etc. processes related to the development and progression of obesity. Leptin, called the satiety hormone, is involved in many vital activities from appetite metabolism to the immune system and is also effective in energy homeostasis. Genetic defects in the signaling or components of the leptin hormone, which plays a major role in the regulation of body weight, may cause leptin resistance and thus obesity. In addition, possible contributions of intestinal microbiota to the pathogenesis of many metabolic disorders such as obesity, insulin resistance are being investigated. Intestinal microbiota; it is responsible for many metabolic events such as food digestion and absorption, regulation of secretion of various appetite hormones or peptides, and disorders in the microbiota are also risk factors for obesity. It is also supported by studies that the intestinal microbiota is associated with leptin, which may have an effect on obesity. This review has been prepared in line with current information researched in order to draw attention to the microbiota and the role of leptin hormone in the etiology of obesity. The research was compiled from publications published in peer-reviewed journals and scanned in PubMed, Web of Science, and Google Scholar. For this purpose, the keywords leptin, intestinal microbiota, obesity, leptin resistance were used together and research articles were included in this study.

Keywords

• Leptin
• Intestinal microbiota
• Obesity
• Leptin resistance
• Microorganism

References

1. 1. Xu Y, Wang N, Tan HY, Li S, Zhang C, Zhang Z, Feng Y. Panax notoginseng saponins modulate the gut microbiota to promote thermogenesis and beige adipocyte reconstruction via leptin-mediated AMPKα/STAT3 signaling in diet-induced obesity. Theranostics. 2020;10(24):11302-11323.
2. 2. Benbaibeche H, Bounihi A, Koceir EA. Leptin level as a biomarker of uncontrolled eating in obesity and overweight. Ir J Med Sci. 2021;190(1):155-161.
3. 3. Keleş V, Büyükgüzel K, Büyükgüzel E. Leptin ve Metabolik Düzenlemedeki Rolü. Türkiye Diyabet ve Obezite Dergisi. 2018; 2(1): 17-22
4. 4. Dornbush S, Aeddula NR. Physiology, Leptin. 2021 Apr 20. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan.
5. 5. Ahima RS. HDAC6 inhibition overcomes leptin resistance in obesity. Nat Metab. 2022 Jan 17. doi: 10.1038/s42255-021- 00500-w. Epub ahead of print.
6. 6. Enriori, P. J.,Evans, A. E., Sinnayah, P., &Cowley, M. A., Leptin resistance and obesity. Obesity. 2006;14(S8):254S-258S.
7. 7. Yetkin İ, Yetiş H, Kayahan Satış N. Bağırsak Mikrobiyotasının İnsülin Direnci, Diabetes Mellitus ve Obezite ile İlişkisi. Türkiye Diyabet ve Obezite Dergisi. 2018; 2(1):1-8.
8. 8. Aksoyalp Z Ş, Nacitarhan C. Diabetes Mellitus’ta Mikrobiyotanın Rolü ve Hedeflenmesi. Türkiye Diyabet ve Obezite Dergisi. 2021; 5(1): 51-58.

9. 9. Durmaz, B. Bağırsak mikrobiyotası ve obezite ile ilişkisi. Turkish Bulletin of Hygiene & Experimental Biology/Türk Hijyen ve Deneysel Biyoloji, 2019; 76(3).
10. 10. Baothman, O. A.,Zamzami, M. A., Taher, I., Abubaker, J., & Abu-Farha, M., The role of gut microbiota in thedevelopment of obesity and diabetes. Lipids in health and disease. 2016;15(1):1-8.
11. 11. Amabebe, E., Robert, F. O., Agbalalah, T., &Orubu, E. S., Microbial dysbiosis-induce dobesity: role of gut microbiota in homoeostasis of energy metabolism. British Journal of Nutrition. 2020; 123(10): 1127-1137
12. 12. Münzberg, H.,&Morrison, C. D., Structure, production and signaling of leptin. Metabolism. 2015; 64(1): 13-23.
13. 13. Tiaka, E. K.,Manolakis, A. C., Kapsoritakis, A. N., & Potamianos, S. P., Unraveling the link between leptin, ghrelin and different types of colitis. Annals of Gastroenterology: Quarterly Publication of the Hellenic Society of Gastroenterology. 2011; 24(1):20.
14. 14. Gruzdeva, O.,Borodkina, D., Uchasova, E., Dyleva, Y. ve Barbarash, O., Leptin resistance: underlying mechanisms and diagnosis. Diabetes, metabolic syndrome and obesity: targets and treatment. 2019; 12: 191.
15. 15. Guo, X., Roberts, M. R., Becker, S. M., Podd, B., Zhang, Y., Chua, S. C., Petri, W. A., Leptin signaling in intestinal epithelium mediates resistance to enteric infection by Entamoeba histolytica. Mucosalimmunology. 2011; 4(3): 294- 303.
16. 16. Mackey-Lawrence, N. M., Petri, W. A., Leptin and mucosal immunity. Mucosal immunology. 2012; 5(5): 472-479.
17. 17. Dominique M, Breton J, Guérin C, Bole-Feysot C, Lambert G, Déchelotte P, Fetissov S. Effects of Macronutrients on the In Vitro Production of ClpB, a Bacterial Mimetic Protein of α-MSH and Its Possible Role in Satiety Signaling. Nutrients. 2019 Sep 5;11(9):2115.
18. 18. Bhaskaran, S.,Pharaoh, G., Ranjit, R., Murphy, A., Matsuzaki, S., Nair, B. C., Deepa, S. S., Loss of mitochondrial protease ClpP protects mice from diet‐induce dobesity and insulinre sistance. EMBO reports. 2018; 19(3):e45009.
19. 19. Bargut TC, Silva-e-Silva AC, Souza-Mello V, Mandarim-de- Lacerda CA, Aguila MB. Mice fed fish oil diet and upregulation of brown adipose tissue thermogenic markers. Eur J Nutr. 2016 Feb;55(1):159-69.
20. 20. Chakraborti, CK., New-found link between microbiota and obesity. World journal of gastrointestinal pathophysiology. 2015; 6(4): 110.
21. 21. Park, H. K., &Ahima, R. S., Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism. Metabolism. 2015; 64(1): 24-34.
22. 22. MyersJr, M. G.,Leibel, R. L., Seeley, R. J., &Schwartz, M. W., Obesity and leptin resistance: distinguishing cause from effect. Trends in Endocrinology&Metabolism. 2010; 21(11):643-651.
23. 23. Cennet, A. K., Bir Adipositokin Üyesi: Leptin. SDÜ Tıp Fakültesi Dergisi. 2016;23(1).
24. 24. Gomes, A. C.,Hoffmann, C., &Mota, J. F., The human gut microbiota: Metabolism and perspective in obesity. Gut microbes. 2018; 9(4):308-325.
25. 25. Palmas V, Pisanu S, Madau V, Casula E, Deledda A, Cusano R, Uva P, Vascellari S, Loviselli A, Manzin A, Velluzzi F. Gut microbiota markers associated with obesity and overweight in Italian adults. Sci Rep. 2021;11(1):5532.
26. 26. Yuan X, Chen R, McCormick KL, Zhang Y, Lin X, Yang X. The role of the gut microbiota on the metabolic status of obese children. Microb Cell Fact. 2021;20(1):53.
27. 27. Saad MJ, Santos A, Prada PO. Linking Gut Microbiota and Inflammation to Obesity and Insulin Resistance. Physiology (Bethesda). 2016 Jul;31(4):283-93.
28. 28. Cani, P. D.,Amar, J., Iglesias, M. A., Poggi, M., Knauf, C., Bastelica, D., .&Burcelin, R., Metabolic endotoxemiainitiates obesity and insulin resistance. Diabetes. 2007; 56(7):1761- 1772.
29. 29. Klancic, T.,&Reimer, R. A., Gut microbiota and obesity: Impact of antibiotics and prebiotics and potential for musculoskeleta lhealth. Journal of sport and health science. 2020; 9(2): 110- 118.
30. 30. Cuevas-Sierra, A.,Ramos-Lopez, O., Riezu-Boj, J. I., Milagro, F. I., &Martinez, J. A., Diet, gut microbiota, and obesity: links with host genetics and epigenetics and potential applications. Advances in Nutrition. 2019; 10(suppl_1): S17-S30.
31. 31. Yao, H., Fan, C., Fan, X., Lu, Y., Wang, Y., Wang, R., &Qi, K., Effects of gut microbiota on leptin expressionand body weigh tarelessened by high-fat diet in mice. British Journal of Nutrition. 2020; 124(4):396-406.