Progesterone-Induced Hyperphagia is Attenuated by Myrica nagi through Dopaminergic and Serotonergic Modulation in Female Mice
Authors
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Department of Pharmacology, Punjab Multipurpose Medical Institute, Sehna, Barnala - 148101, Punjab ,IN
Yash Prashar -
Department of Pharmacology, Shree S. K. Patel College of Pharmaceutical Education and Research, Ganpat University, Ganpat Vidyanagar, Mehsana-Gozaria Highway, Kherva - 384012, Gujarat ,INNilesh J. Patel
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Chitkara School of Health Sciences, Chitkara University, Rajpura - 140401, Punjab ,INDeepanshi Sharma
DOI:
https://doi.org/10.18311/ti/2023/v30i4/34631Keywords:
Anti-Obesity Agent, Dopamine, Feeding Behavior, Hyperphagia, Herbal Extract, Progesterone-Induced Obesity, SerotoninAbstract
Regulation of feeding behavior to control obesity is an alternative line of research for the treatment of obesity and diabetes. Compared to other models of obesity, the progesterone-induced obesity model is more specific to the female population; it focuses on the eating behavior and behavioral and emotional changes associated with progesterone. We aimed to study the changes in feeding behavior upon progesterone administration and the effects of Myrica nagi Thunb (Myricaceae) extracts on these changes. Further, this study aimed to provide insights into the progesterone-induced hyperphagia modulated by serotonergic and dopaminergic systems. In this study, experimental obesity was induced in female mice by treating with a high dose of progesterone for 28 days (sub-chronic study) followed by the assessment of parameters such as food consumption behavior, behavioral parameters including ambulatory movements, rearing, and grooming, and biochemical parameters such as lipid profile (total cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein), liver parameters (alkaline phosphatase and serum glutamic pyruvic transaminase), serotonin and dopamine levels, and liver histopathology. The sub-chronic administration of progesterone, via the subcutaneous route, induced significant hyperphagia and promoted fat accumulation. Even though we did not find significant differences in food intake between mice in the control group and progesterone-treated groups, the final weight in the progesterone-administered groups increased, signifying the impact of this progesterone-induced obesity model. Treatment with MEMN extract reversed the progesterone-induced effects suggesting that herbal extracts can be exploited as serotonergic and dopaminergic agents for the treatment of progesterone-induced eating disorders, especially in the female population.
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Copyright (c) 2023 Yash Prashar, Nilesh J. Patel, Deepanshi Sharma
This work is licensed under a Creative Commons Attribution 4.0 International License.
Accepted 2023-10-04
Published 2023-11-21
References
Holmberg E, Sjöstedt J, Malinina E, Johansson M, Turkmen S, Ragagnin G, et al. Allopregnanolone involvement in feeding regulation, overeating and obesity. Front Neuroendocrinol. 2018; 48:70-7. https://doi.org/10.1016/j. yfrne.2017.07.002 DOI: https://doi.org/10.1016/j.yfrne.2017.07.002
Pinheiro Volp AC, Esteves de Oliveira FC, Duarte Moreira Alves R, Esteves EA, Bressan J. Energy expenditure: Components and evaluation methods. Nutr Hosp. 2011; 26:430-40. http:// dx.doi.org/10.1590/S0212-16112011000300002
Levine JA. Non-Exercise Activity Thermogenesis (NEAT). Nutr Rev. 2004; 62:S82-97. https://doi. org/10.1111/j.1753-4887.2004.tb00094.x DOI: https://doi.org/10.1111/j.1753-4887.2004.tb00094.x
Kretschmer BD, Schelling P, Beier N, Liebscher C, Treutel S, Krüger N, et al. Modulatory role of food, feeding regime and physical exercise on body weight and insulin resistance. Life Sci. 2005; 76:1553-73. https://doi.org/10.1016/j.lfs.2004.08.028 DOI: https://doi.org/10.1016/j.lfs.2004.08.028
Galaly SR, Hozayen WG, Amin KA, Ramadan SM. Effects of Orlistat and herbal mixture extract on brain, testes functions and oxidative stress biomarkers in a rat model of high-fat diet. Beni Suef Univ J Basic Appl Sci. 2014; 3:93- 105. https://doi.org/10.1016/j.bjbas.2014.05.002 DOI: https://doi.org/10.1016/j.bjbas.2014.05.002
Ozkan Y, Aydin S, Donder E, Koca SS, Aydin S, Ozkan B, et al. Effect of orlistat on the total ghrelin and leptin levels in obese patients. J Physiol Biochem. 2009; 65:215-23. https://doi.org/10.1007/BF03180574 DOI: https://doi.org/10.1007/BF03180574
Chidrawar VR, Patel KN, Sheth NR, Shiromwar SS, Trivedi P. Antiobesity effect of Stellaria media against drug induced obesity in Swiss albino mice. Ayu. 2011; 32:576-84. https://doi.org/10.4103/0974-8520.96137 DOI: https://doi.org/10.4103/0974-8520.96137
Kaur G, Kulkarni SK. Evidence for serotonergic modulation of progesterone-induced hyperphagia, depression and algesia in female mice. Brain Res. 2002; 943:206-15. https://doi.org/10.1016/S0006-8993(02)02624-0 DOI: https://doi.org/10.1016/S0006-8993(02)02624-0
Berenson AB, Rahman M. Changes in weight, total fat, percent body fat, and central-to-peripheral fat ratio associated with injectable and oral contraceptive use. Am J Obstet Gynecol. 2009; 200:329.e1-8. https://doi.org/10.1016/j.ajog.2008.12.052 DOI: https://doi.org/10.1016/j.ajog.2008.12.052
Halford JC, Harrold JA, Lawton CL, Blundell JE. Serotonin (5-HT) drugs: Effects on appetite expression and use for the treatment of obesity. Curr Drug Targets. 2005; 6:201- 13. https://doi.org/10.2174/1389450053174550 DOI: https://doi.org/10.2174/1389450053174550
Lam DD, Garfield AS, Marston OJ, Shaw J, Heisler LK. Brain serotonin system in the coordination of food intake and body weight. Pharmacol Biochem Behav. 2010; 97:84- 91. https://doi.org/10.1016/j.pbb.2010.09.003 DOI: https://doi.org/10.1016/j.pbb.2010.09.003
Hesse S, van de Giessen E, Zientek F, Petroff D, Winter K, Dickson JC, et al. Association of central serotonin transporter availability and body mass index in healthy Europeans. Eur Neuro Psycho Pharmacol. 2014; 24:1240- 47. https://doi.org/10.1016/j.euroneuro.2014.05.005 DOI: https://doi.org/10.1016/j.euroneuro.2014.05.005
Meguid MM, Fetissov SO, Varma M, Sato T, Zhang L, Laviano A, et al. Hypothalamic dopamine and serotonin in the regulation of food intake. Nutrition. 2000; 16:843-57. https://doi.org/10.1016/S0899-9007(00)00449-4 DOI: https://doi.org/10.1016/S0899-9007(00)00449-4
Donovan MH, Tecott LH. Serotonin and the regulation of mammalian energy balance. Front Neurosci. 2013; 7:36. https://doi.org/10.3389/fnins.2013.00036 DOI: https://doi.org/10.3389/fnins.2013.00036
la Fleur SE, Serlie MJ. The interaction between nutrition and the brain and its consequences for body weight gain and metabolism; studies in rodents and men. Best Pract Res Clin Endocrinol Metab. 2014; 28:649-59. https://doi. org/10.1016/j.beem.2014.06.001 DOI: https://doi.org/10.1016/j.beem.2014.06.001
Blum K, Thanos PK, Gold MS. Dopamine and glucose, obesity, and reward deficiency syndrome. Front Psychol. 2014; 5:919. https://doi.org/10.3389/fpsyg.2014.00919 DOI: https://doi.org/10.3389/fpsyg.2014.00919
Stice E, Spoor S, Bohon C, Small DM. Relation between obesity and blunted striatal response to food is moderated by TaqIA A1 allele. Science. 2008; 322:449-52. https://doi. org/10.1126/science.1161550 DOI: https://doi.org/10.1126/science.1161550
Johnson PM, Kenny PJ. Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. Nat Neurosci. 2010; 13:635-41. https://doi. org/10.1038/nn.2519 DOI: https://doi.org/10.1038/nn.2519
German-Ponciano LJ, Rosas-Sánchez GU, Rivadeneyra- Domínguez E, Rodríguez-Landa JF. Advances in the preclinical study of some flavonoids as potential antidepressant agents. Scientifica (Cairo). 2018; 2018:2963565. https://doi.org/10.1155/2018/2963565 DOI: https://doi.org/10.1155/2018/2963565
Sood P, Shri R. A review on ethnomedicinal, phytochemical and pharmacological aspects of Myrica esculenta. Indian J Pharm Sci. 2018; 80:2-13. https://doi.org/10.4172/ pharmaceutical-sciences.1000325 DOI: https://doi.org/10.4172/pharmaceutical-sciences.1000325
Panthari P, Kharkwal H, Kharkwal H, Joshi DD. Myrica nagi: A review on active constituents, biological and therapeutic effects. Int J Pharm Sci. 2012; 4:38-42
Sikarwar MS. Formulation and evaluation of some Indian medicinal plants for antidiabetic and antihyperlipidemic activity. [dissertation]. University’s location: KLE University; 2011.
Debiyi OO, Sofowora FA. Phytochemical screening of medical plants. Iloyidia. 1978; 3:234-46.
Trease GE, Evans WC, Evans D. Trease and Evans Pharmacognosy. 16th ed. New York: Saunders/Elsevier; 2009. p. 119-59.
Kokate CK, Purohit AP, Gokhale SB. Pharmacognosy. India: Nirali Prakashan; 2006. p. 493-7.
Gundamaraju R, Mulaplli SB, Ramesh C. Evaluation of anti-obesity activity of Lantana camara var Linn. by progesterone-induced obesity on albino mice. Int J Pharmacogn Phytochem Res. 2013; 4:213-18.
OECD. Test No. 423: Acute oral toxicity - Acute toxic class method. OECD Guidelines for the Testing of Chemicals, Section 4, Paris: OECD Publishing; 2002. p. 1-14.
Fernstron JD, Wurtman RJ. Brain serotonin content: increase following ingestion of carbohydrate diet. Science. 1971; 174:1023-5. https://doi.org/10.1126/science.174.4013.1023 DOI: https://doi.org/10.1126/science.174.4013.1023
Schlumpf M, Lichtensteiger W, Langemann H, Waser PG, Hefti F. A fluorometric micro method for the simultaneous determination of serotonin, noradrenaline and dopamine in milligram amounts of Brain tissue. Biochem Pharmacol. 1974; 23:2437-46. https://doi.org/10.1016/0006- 2952(74)90235-4 DOI: https://doi.org/10.1016/0006-2952(74)90235-4
Costa E, Guidotti A. Diazepam Binding Inhibitor (DBI): A peptide with multiple biological actions. Life Sci. 1991; 49:325-44. https://doi.org/10.1016/0024-3205(91)90440-M DOI: https://doi.org/10.1016/0024-3205(91)90440-M
World Health Organization. Obesity: Preventing and managing the global epidemic. Report of a WHO consultation (WHO Technical Report Series 894). Geneva: World Health Organization; 2000.
Dixon JB. The effect of obesity on health outcomes. Mol Cell Endocrinol. 2010; 316:104-8. https://doi.org/10.1016/j. mce.2009.07.008 DOI: https://doi.org/10.1016/j.mce.2009.07.008
Schumacher M, Mattern C, Ghoumari A, Oudinet JP, Liere P, Labombarda F, et al. Revisiting the roles of progesterone and allopregnanolone in the nervous system: Resurgence of the progesterone receptors. Prog Neurobiol. 2014; 113:6-39. https://doi.org/10.1016/j.pneurobio.2013.09.004 DOI: https://doi.org/10.1016/j.pneurobio.2013.09.004
Saito K, Matsuzaki T, Iwasa T, Miyado M, Saito H, Hasegawa T, et al. Steroidogenic pathways involved in androgen biosynthesis in eumenorrheic women and patients with polycystic ovary syndrome. J Steroid Biochem Mol Biol. 2016; 158:31-7. https://doi.org/10.1016/j.jsbmb.2016.02.010 DOI: https://doi.org/10.1016/j.jsbmb.2016.02.010
Rouge-Pont F, Mayo W, Marinelli M, Gingras M, Le Moal M, Piazza PV. The neurosteroid allopregnanolone increases dopamine release and dopaminergic response to morphine in the rat nucleus accumbens. Eur J Neurosci. 2002; 16:169-73. https://doi.org/10.1046/j.1460-9568.2002.02084.x DOI: https://doi.org/10.1046/j.1460-9568.2002.02084.x
Prashar Y, Patel NJ. An in vitro approach to evaluate the anti-adipogenic effect of Myrica nagi Thunb. Fruit extract on 3T3-L1 adipocyte cell line. Obes Med. 2020; 18:100228. https://doi.org/10.1016/j.obmed.2020.100228 DOI: https://doi.org/10.1016/j.obmed.2020.100228
Bethea CL, Gundlah C, Mirkes SJ. Ovarian steroid action in the serotonin neuronal system of females. J Pediatric Adoles Gynecol. 1997; 10:18-23.
Reddy DS, Kulkarni SK. The role of GABA-A and mitochondrial diazepam-binding inhibitor receptors on the effects of neurosteroids on food intake in mice. Psychopharmacology (Berl). 1998; 137:391-400. https:// doi.org/10.1007/s002130050635 DOI: https://doi.org/10.1007/s002130050635
Mandour T, Kissebah AH, Wynn V. Mechanism of estrogen and progesterone effects on lipid and carbohydrate metabolism: Alteration in the insulin: Glucagon molar ratio and hepatic enzyme activity. Eur J Clin Invest. 1977; 7:181- 7. https://doi.org/10.1111/j.1365-2362.1977.tb01595.x DOI: https://doi.org/10.1111/j.1365-2362.1977.tb01595.x
Amatayakul K, Sivasomboon B, Thanangkul O. A study of the mechanism of weight gain in medroxyprogesterone acetate users. Contraception. 1980; 22:605-22. https://doi. org/10.1016/0010-7824(80)90087-6 DOI: https://doi.org/10.1016/0010-7824(80)90087-6
Sinchak K, Wagner EJ. Estradiol signaling in the regulation of reproduction and energy balance. Front Neuroendocrinol. 2012; 33:342-63. https://doi. org/10.1016/j.yfrne.2012.08.004 DOI: https://doi.org/10.1016/j.yfrne.2012.08.004
Mani S, Portillo W. Activation of progestin receptors in female reproductive behavior: Interactions with neurotransmitters. Front Neuroendocrinol. 2010; 31:157-71. https://doi. org/10.1016/j.yfrne.2010.01.002 DOI: https://doi.org/10.1016/j.yfrne.2010.01.002
Haddad-Tóvolli R, Dragano NRV, Ramalho AFS, Velloso LA. Development and function of the blood-brain barrier in the context of metabolic control. Front Neurosci. 2017; 11:224. https://doi.org/10.3389/fnins.2017.00224 DOI: https://doi.org/10.3389/fnins.2017.00224
Austin J, Marks D. Hormonal regulators of appetite. Int J Pediatr Endocrinol. 2008; 2009:141753. https://doi.org/10.1155/2009/141753 DOI: https://doi.org/10.1186/1687-9856-2009-141753
Lee B, Shao J. Adiponectin and energy homeostasis. Rev Endocr Metab Disord. 2014; 15:149-56. https://doi.org/10.1007/s11154-013-9283-3 DOI: https://doi.org/10.1007/s11154-013-9283-3
Gong X, Liu Y, Wang X, et al. Progesterone-induced obesity: Mechanisms and therapeutic strategies. Front Endocrinol (Lausanne). 2023; 14:852286.
Xu L, Zhang X, Zhou X, et al. Progesterone promotes obesity through the AMPK pathway in mice. J Endocrinol. 2023; 240(3):100047.
