Genetic features of hormonal regulation of energy metabolism (literature review)

Keywords: obesity, leptin, LEPR, POMC, MC4R, mutations

Abstract

Summary: Many chronic diseases are associated with impaired human energy metabolism and its hormonal regulation. According to the WHO, there are more than 300 million people with obesity in the world, 24.1% of the population are suffering from obesity in Ukraine. Being overweight is one of the main factors in the development of type 2 diabetes, cardiovascular and oncological diseases, pathology of the musculoskeletal and digestive systems, as well as reproductive dysfunction. Obesity is a multifactorial disease. According to the results presented in the literature, the accumulation of fat in the subcutaneous and visceral region will lead to a change in the expression of genes encoding proteins that regulate energy metabolism. Leptin belongs to the group of adipocyte hormones of subcutaneous fat. The expression of leptin is regulated by several hormones, including insulin and glucocorticoids, and starvation also leads to a decrease of leptin concentration in plasma. Leptin reduces hunger, activates the use of fats in energy metabolism and inhibits the excessive accumulation of fat reserves. Leptin resistance may occur due to the presence of a mutation or polymorphic variation in its receptor gene. One of the most studied and clinically significant polymorphic variants of the leptin receptor gene (LEPR) is the replacement of glutamine amino acid with arginine at 223 positions (Q223R), which leads to a decrease in the sensitivity of receptors to leptin. Mutations in POMC lead to obesity, which is accompanied by atrophy of the adrenal cortex and multiple disorders. Mutations in MC4R lead to obesity in patients but ensure normal sexual development and adequate functioning of the endocrine glands. Now scientists on the whole world are actively developing methods to fight obesity, based on stimulating the functioning of cascades of leptin-dependent signaling

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Author Biographies

Taisiia Sazonova, , student of the School of Medicine of V.N. Karazin Kharkiv National University

Freedom Square, 4, Kharkiv, Ukraine, 61022

Olena Khrystenko, endocrinologist, Kharkov city polyclinic №8

61074, Kharkiv, Klochkivska str., h 295, apt. 35

Olena Fedota, Doctor of Biological Sciences, Professor, Department of Obstetrics and Gynecology of V.N. Karazin Kharkiv National University

Freedom Square, 6, Kharkiv, Ukraine, 61022

References

Yang, L., & Colditz, G. A. (2015). Prevalence of overweight and obesity in the United States, 2007-2012. JAMA internal medicine, 175(8), 1412-1413.

Skinner, A. C., Ravanbakht, S. N., Skelton, J. A., Perrin, E. M., & Armstrong, S. C. (2018). Prevalence of obesity and severe obesity in US children, 1999–2016. Pediatrics, 141(3), e20173459.

Alamuddin, N., Bakizada, Z., & Wadden, T. A. (2016). Management of obesity. Journal of Clinical Oncology, 34(35), 4295-4305.

Vilchis-Gil, J., Galván-Portillo, M., Klünder-Klünder, M., Cruz, M., & Flores-Huerta, S. (2015). Food habits, physical activities and sedentary lifestyles of eutrophic and obese school children: a case–control study. BMC public health, 15(1), 124.

Popovic-Lipovac, A., & Strasser, B. (2015). A review on changes in food habits among immigrant women and implications for health. Journal of immigrant and minority health, 17(2), 582-590.

Hemmingsson, E. (2018). Early childhood obesity risk factors: socioeconomic adversity, family dysfunction, offspring distress, and junk food self-medication. Current obesity reports, 7(2), 204-209.

Isachenkova, O. G. A. (2015). Eating behavior as an important factor in the development of obesity and comorbid diseases. Obesity and metabolism, 12(4), 14-17.

Nguyen, J. (2018). Childhood Obesity: United States.

Lam, U. (2018). How To Prevent Childhood Obesity.

Blüher, M. (2019). Obesity: global epidemiology and pathogenesis. Nature Reviews Endocrinology, 1.

Oussaada, S. M., van Galen, K. A., Cooiman, M. I., Kleinendorst, L., Hazebroek, E. J., van Haelst, M. M., ... & Serlie, M. J. (2019). The pathogenesis of obesity. Metabolism, 92, 26-36.

Samaras, K., Tevaearai Stahel, H., Goldman, M., le Coutre, J., & Holly, J. M. (2019). With Obesity Becoming the New Normal, What Should We Do?. Frontiers in endocrinology, 10, 250.

American Diabetes Association. (2019). 8. Obesity management for the treatment of type 2 diabetes: Standards of Medical Care in Diabetes—2019. Diabetes Care, 42(Supplement 1), S81-S89.

Ferguson, L. D., & Sattar, N. (2019). Impact of Obesity on Cardiovascular Disease. Obesity: Pathogenesis, Diagnosis, and Treatment, 273-293.

Li, L., Chen, K., Wang, A. P., Gao, J. Q., Zhao, K., Wang, H. B., ... & Yang, L. L. (2019). Cardiovascular disease outcomes in metabolically healthy obesity in communities of Beijing cohort study. International journal of clinical practice, 73(3), e13279.

Snider, A. P., & Wood, J. R. (2019). Obesity Induces Ovarian Inflammation and Reduces Oocyte Quality. Reproduction, 1(aop).

van der Valk, E. S., van den Akker, E. L., Savas, M., Kleinendorst, L., Visser, J. A., Van Haelst, M. M., ... & van Rossum, E. F. (2019). A comprehensive diagnostic approach to detect underlying causes of obesity in adults. Obesity Reviews, 20(6), 795-804.

Leeners, B., Geary, N., Tobler, P. N., & Asarian, L. (2017). Ovarian hormones and obesity. Human reproduction update, 23(3), 300-321.

Hendricks, A. E., Bochukova, E. G., Marenne, G., Keogh, J. M., Atanassova, N., Bounds, R., ... & Muddyman, D. (2017). Rare variant analysis of human and rodent obesity genes in individuals with severe childhood obesity. Scientific reports, 7(1), 4394.

Sáinz, N., Barrenetxe, J., Moreno-Aliaga, M. J., & Martínez, J. A. (2015). Leptin resistance and diet-induced obesity: central and peripheral actions of leptin. Metabolism, 64(1), 35-46.

Hosoi, T., Kohda, T., Matsuzaki, S., Ishiguchi, M., Kuwamura, A., Akita, T., ... & Ozawa, K. (2016). Key role of heat shock protein 90 in leptin‐induced STAT3 activation and feeding regulation. British journal of pharmacology, 173(15), 2434-2445.

Park, H. K., & Ahima, R. S. (2015). Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism. Metabolism, 64(1), 24-34.

Wrann, C. D., Eguchi, J., Bozec, A., Xu, Z., Mikkelsen, T., Gimble, J., ... & Rosen, E. D. (2012). FOSL2 promotes leptin gene expression in human and mouse adipocytes. The Journal of clinical investigation, 122(3).

Mora-Muñoz, L., Guerrero-Naranjo, A., Rodríguez-Jimenez, E. A., Mastronardi, C. A., & Velez-van-Meerbeke, A. (2018). Leptin: role over central nervous system in epilepsy. BMC neuroscience, 19(1), 1-9.

Ahima, R. S., Prabakaran, D., Mantzoros, C., Qu, D., Lowell, B., Maratos-Flier, E., & Flier, J. S. (1996). Role of leptin in the neuroendocrine response to fasting. Nature, 382(6588), 250.

Abella, V., Scotece, M., Conde, J., Pino, J., Gonzalez-Gay, M. A., Gomez-Reino, J. J., ... & Gualillo, O. (2017). Leptin in the interplay of inflammation, metabolism and immune system disorders. Nature Reviews Rheumatology, 13(2), 100.

You, Z. B., Wang, B., Gardner, E. L., & Wise, R. A. (2019). Cocaine and cocaine expectancy increase growth hormone, ghrelin, GLP-1, IGF-1, adiponectin, and corticosterone while decreasing leptin, insulin, GIP, and prolactin. Pharmacology Biochemistry and Behavior, 176, 53-56.

Dodd, G. T., Decherf, S., Loh, K., Simonds, S. E., Wiede, F., Balland, E., ... & Neel, B. G. (2015). Leptin and insulin act on POMC neurons to promote the browning of white fat. Cell, 160(1-2), 88-104.

Zhang, Z. Y., Dodd, G. T., & Tiganis, T. (2015). Protein tyrosine phosphatases in hypothalamic insulin and leptin signaling. Trends in pharmacological sciences, 36(10), 661-674.

Hommel, J. D., Trinko, R., Sears, R. M., Georgescu, D., Liu, Z. W., Gao, X. B., ... & DiLeone, R. J. (2006). Leptin receptor signaling in midbrain dopamine neurons regulates feeding. neuron, 51(6), 801-810.

Tartaglia, L. A., Dembski, M., Weng, X., Deng, N., Culpepper, J., Devos, R., ... & Muir, C. (1995). Identification and expression cloning of a leptin receptor, OB-R. Cell, 83(7), 1263-1271.

dos Santos Rocha, A., de Cássia Ribeiro-Silva, R., Nunes de Oliveira Costa, G., Alexandrina Figueiredo, C., Cunha Rodrigues, L., Maria Alvim Matos, S., ... & Lima Barreto, M. (2018). Food Consumption as a Modifier of the Association between LEPR Gene Variants and Excess Body Weight in Children and Adolescents: A Study of the SCAALA Cohort. Nutrients, 10(8), 1117.

Clement, K., Vaisse, C., Lahlou, N., Cabrol, S., Pelloux, V., Cassuto, D., ... & Basdevant, A. (1998). A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature, 392(6674), 398.

Ghali, Z. H., Ahmed, I. H., Gorshunska, M. Y., Pоchеrnyaev, A. K., & Atramentova, L. A. (2012). Structure of Ukrainian population on SNP rs1137101 of leptin receptor gene LEPR. The Journal of V.N. Karazin Kharkiv National University. Series: biology, (15), 94-98.

Ahmed, I. H., & Ghali, Z. H. (2017). SNP rs1137101 Leptin Receptor Gene LEPR as a Risk Factor for Type 2 Diabetes. American Scientific Research Journal for Engineering, Technology, and Sciences (ASRJETS), 38(2), 341-347.

Loos, R. J., Lindgren, C. M., Li, S., Wheeler, E., Zhao, J. H., Prokopenko, I., ... & Berndt, S. I. (2008). Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nature genetics, 40(6), 768.

Kühnen, P., Handke, D., Waterland, R. A., Hennig, B. J., Silver, M., Fulford, A. J., ... & Hinney, A. (2016). Interindividual variation in DNA methylation at a putative POMC metastable epiallele is associated with obesity. Cell metabolism, 24(3), 502-509.

Ibars, M., Ardid-Ruiz, A., Suárez, M., Muguerza, B., Bladé, C., & Aragonès, G. (2017). Proanthocyanidins potentiate hypothalamic leptin/STAT3 signalling and Pomc gene expression in rats with diet-induced obesity. International Journal of Obesity, 41(1), 129.

Resende, C. M. M., Durso, D. F., Borges, K. B. G., Pereira, R. M., Rodrigues, G. K. D., Rodrigues, K. F., ... & Alvarez-Leite, J. I. (2018). The polymorphism rs17782313 near MC4R gene is related with anthropometric changes in women submitted to bariatric surgery over 60 months. Clinical Nutrition, 37(4), 1286-1292.

Le Beyec-Le Bihan, J., Poitou-Bernert, C., Karsenty, A., Pelloux, V., Lacorte, J. M., Tounian, P., ... & Dubern, B. (2019, May). Variants in genes of the leptin/melanocortin pathway are involved in 3% of cases of early-onset severe obesity. In 21st European Congress of Endocrinology (Vol. 63). BioScientifica.

Siljee, J. E., Wang, Y., Bernard, A. A., Ersoy, B. A., Zhang, S., Marley, A., ... & Vaisse, C. (2018). Subcellular localization of MC4R with ADCY3 at neuronal primary cilia underlies a common pathway for genetic predisposition to obesity. Nature genetics, 50(2), 180.

Wadden, T. A., & Bray, G. A. (Eds.). (2018). Handbook of obesity treatment. Guilford Publications.

Olson, K. (2017). Behavioral approaches to the treatment of obesity. Rhode Island Medical Journal, 100(3), 21.

Fitzpatrick, S. L., Wischenka, D., Appelhans, B. M., Pbert, L., Wang, M., Wilson, D. K., & Pagoto, S. L. (2016). An evidence-based guide for obesity treatment in primary care. The American journal of medicine, 129(1), 115-e1.

Chao, A. M., Wadden, T. A., Tronieri, J. S., Pearl, R. L., Alamuddin, N., Bakizada, Z. M., ... & Berkowitz, R. I. (2019). Effects of addictive-like eating behaviors on weight loss with behavioral obesity treatment. Journal of behavioral medicine, 42(2), 246-255.

Paz-Filho, G., Mastronardi, C. A., & Licinio, J. (2015). Leptin treatment: facts and expectations. Metabolism, 64(1), 146-156.

Ottaway, N., Mahbod, P., Rivero, B., Norman, L. A., Gertler, A., D’Alessio, D. A., & Perez-Tilve, D. (2015). Diet-induced obese mice retain endogenous leptin action. Cell metabolism, 21(6), 877-882.

Quarta, C., Sánchez-Garrido, M. A., Tschöp, M. H., & Clemmensen, C. (2016). Renaissance of leptin for obesity therapy. Diabetologia, 59(5), 920-927.

Szewczyk‐Golec, K., Woźniak, A., & Reiter, R. J. (2015). Inter‐relationships of the chronobiotic, melatonin, with leptin and adiponectin: implications for obesity. Journal of pineal research, 59(3), 277-291.

Wabitsch, M., Funcke, J. B., Lennerz, B., Kuhnle-Krahl, U., Lahr, G., Debatin, K. M., ... & Fischer-Posovszky, P. (2015). Biologically inactive leptin and early-onset extreme obesity. New England Journal of Medicine, 372(1), 48-54.

Altirriba, J., Poher, A. L., & Rohner-Jeanrenaud, F. (2015). Chronic oxytocin administration as a treatment against impaired leptin signaling or leptin resistance in obesity. Frontiers in endocrinology, 6, 119.

Published
2019-11-30
How to Cite
Sazonova, T., Khrystenko, O., & Fedota, O. (2019). Genetic features of hormonal regulation of energy metabolism (literature review). Actual Problems of Modern Medicine, (4). https://doi.org/10.26565/2617-409X-2019-4-02