The Effect of Estrogen Hormone on Leptin Receptor in Small Intestine of Ovariectomized Rats

Main Article Content

Özlem Özden Akkaya
Korhan Altunbaş

Abstract

Objective: Leptin, a 16 kDa hormone encoded by the obese (Ob) gene, is known for its role in regulating food intake, body composition, and energy expenditure. Leptin receptor expression has been demonstrated in several tissues, including the small intestine. Weight gain may occur in humans after menopause or in animals following ovariectomy. Estrogen affects leptin and leptin receptor expressions. In this study, we aimed to contribute to the etiology of obesity by investigating the effects of E2 on leptin receptors in the small intestines of ovariectomized rats as a model of postmenopausal conditions.


Materials and Methods: Bilateral ovariectomy was performed on 6-month-old Sprague-Dawley female rats. Ovariectomized rats (Ovx) were injected with 0.2 ml of sesame oil/rat/day or E2 (25 µg/rat/day) and euthanized at the 18th, 90th, or 162nd hours. Duodenum, jejunum, and ileum samples were fixed and embedded in paraffin using standard methods. The expression of leptin receptors were detected in the small intestine through immunohistochemistry.


Results: Leptin receptor expression was found in the villi and crypt epithelium of the small intestine and in Brunner’s gland of the duodenum. E2 administration increased the leptin receptor expressions on the epithelium of villi and crypt in the duodenum and jejunum at the 90th hour (p<0.05); ileum at the 18th hour (p<0.05); and also on the epithelium of villi in the duodenum at the 162nd hour (p<0.05).


Conclusion: Our results indicate that E2 may upregulate the expression of leptin receptors in the small intestine, where glucose and other nutrients are absorbed after food intake and digestion, depending on the timing.

Downloads

Download data is not yet available.

Article Details

How to Cite
Özden Akkaya, Özlem, & Altunbaş, K. . (2023). The Effect of Estrogen Hormone on Leptin Receptor in Small Intestine of Ovariectomized Rats. Medical Science and Discovery, 10(9), 712–721. https://doi.org/10.36472/msd.v10i9.1010 (Original work published September 27, 2023)
Section
Research Article
Received 2023-08-05
Accepted 2023-09-20
Published 2023-10-17

References

Hamilton BS, Paglia D, Kwan AYM, Deitel M. Increased obes mRNA expression in omental fat cells from massively obese humans. Nature Med 1995;1:953-6.

Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the Mouse obese geneand its human homologue. Nature 1994;372: 425-32.

Halaas JL, Gajawala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, Lallone, RL, Burley SK, Friedman JM. Weight – reducing effects of the plasma protein encoded by the obese gene. Science 1995;269:543-6.

Pelleymounter MA, Cullen MY, Baker MB. Effects of the obese gene product on body weight regulation in ob/ob mice. Science 1995;269:540-3.

Friedman JM, Halas JL. Leptin and the regulation of body weight in mammals. Nature 1998;395:763-9.

Hassink SG, de Lancey E, Sheslow DV, Smith-Kirwin SM, O'Connor DM, Considine RV, Opentanova I, Dostal K, Spear ML, Leef K, Ash M, Spitzer AR, Funanage VL. Placental leptin: an important new growth factor in intrauterine and neonatal development? Pediatrics 1997;100: E1.

Gonzalez RR, Caballero-Campo P, Jasper M, Mercader A, Devoto L, Pellicer A, Simon C. Leptin and Leptin Receptor Are Expressed in the Human endometrium and endometrial leptin secretion is regulated by the human blastocyst. J Clin Endocrinol Metab 2000; 85(12):4883-8.

Wang J, Lie R, Hawkins M, Barzalai N, Rosetti L. A nutrient – sensing pathway regulates leptin gene expression in muscle and fat. Nature 1998;393:684-8.

Casabielle X, Hawkins M, Tome MA, Peino R, Dieguez C, Casanueava FF. Presence of leptin in colostrum and/or breast milk from lactating mothers: a 63 potential role in the regulation of neonatal food intake. J Clin Endocrinol Metab 1997;8: 4270-3.

Cinti S, Matteis RD, Pico C, Ceresi E, Obrador A, Maffeis C, Oliver J, Palou A. Secretory granules of endocrine and chief cells of human stomach mucosa contain leptin Int J Obes Relat Metab Disord 2000;24;789-93.

Mix H, Widjaja A, Jandl O. Expression leptin and leptin receptor isoforms in the human stomach. Gut 2000;47:481-6.

Cammisotto PG, Renaud C, Gingras D, Delvin E, Levy E, Bendayan M. Endocrine and exocrine of leptin by the gastric mucosa. J Histochem Cytochem 2005; 53(7);851-860.

Sobhani I, Bado A, Visszaine C, Buyse M, Kermorgant S, Laigneau JP, Attoub S, Lehy T, Henin D, Mignon M, Lewin MJ. Leptin secretion leptin receptor in the human stomach. Gut 2000;47:178-83.

Bado A, Sandrine L, Samir A, Kermorgant S, Laigneau JP, Bortoluzzi MN, Moizo L, Lehy T, Guerre-Millo M, Le Marchand-Brustel Y, Lewin MJ. The stomach is a source of leptin. Nature 1998;394:790-3

Lostao M.P, Urdaneta E, Martinez –Anso E, Barber A, Martinez JA. Presence of leptin receptor in rat small intestine and leptin effect on sugar absorption. FEBS Lett 1998;423;302-6.

Morton NM, Emilsson V, Liu YL, Cawthorne MA. Leptin action in intestinal cells. J Biol Chem 1998;273:40, 26194-201.

Buyse M, Berlioz F, Guilmeau S, Tsocas A, Voisin T, Péranzi G, Merlin D, Laburthe M, Lewin MJ, Rozé C, Bado A. PepT1-mediated epithelial transport of dipeptides and cephalexin is enhanced by luminal leptin in the small intestine. J Clin Invest. 2001:108(10): 1483-94.

Tartaglia LA, Dembski M, Weng X, Deng NH, Culpepper J, Devos R, Richards GJ, Campfield LA, Clark FT, Deeds J, Muir C, Sanker S, Moriarty A, Moore KJ, Smutko JS, Mays GG, Wool EA, Monroe CA, Tepper RI. İdentification and expression cloning of a leptin receptor, OB-R. Cell 1995;83:1263-71.

Barrenetxe J, Villaro AC, Guembe L, Pascual I, Munoz-Navas M, Barber A, Lostao MP. Distribution of the long leptin receptor isoform in brush border, basolateral membrane, and cytoplasm of enterocytes. Gut 2002;50:797-802.

Sferra R, Pompili S, Cappariello A, Gaudio E, Latella G, Vetuschi A. Prolonged Chronic Consumption of a High Fat with Sucrose Diet Alters the Morphology of the Small Intestine. Int J Mol Sci 2021;22(14):7280.

Yildiz M, Altunbas K. Effect of 17β-oestradiol on the leptin receptor expression in the colon of ovariectomized rats. Revue Méd Vét 2013;164(10):457-63.

Wolinski J, Biernat M, Guilloteau P, Westrom BR, Zabielski R. Exogenous leptin controls the develop.ment of the small intestinein neonatal piglets. J Endocrinol. 2003;177:215-22.

Alavi K, Schwartz MZ, Prasad R, O'connor D, Funanage V. Leptin: a new growth factor for the small intestine. J Pediatr Surg 2002;37:327-30.

Alonso A, Fernandez R, Moreno M, Ordonez P, Diaz F, Gonzalez C. Leptin and its receptor are controlled by 17beta- estradiol in peripheral tissue of ovariectomized rats. Exp Biol Med 2007;232:542-549.

Chen HP, Fan J, Cui S. Detection and estrogen regulation of leptin receptor expression in rat dorsal root gangliyon. Histochem Cell Biol 2006;126:363-9.

Meli R, Pacilio M, Mattace G, Esposito E, Coppola A, Nasti A, Di Carlo C, Nappi C, Di Carlo R. Estrogen and raloxifene modulates leptin and its receptor in hypothalamus and adipose tissue from ovariectomized rats. Endocrinology 2004;145:3115-21.

Shimizu H, Shimomura Y, Nakanishi Y, Futawatari T, Ohtani K, Sato N, Mori M. Estrogen increases invivo leptin production in rats and human subject. J Endocrinol 1997;154:285-92

Thorn SR, Meyer MJ, Van Amburgh ME, Boisclair YR. Effect of estogen on leptin and expression of leptin receptor transcripts in prepubertal dairy heifers. J Dairy Sci 2007;90:3742-50.

Machinal F, Dieudonne MN, Leneveu MC, Pecquery R, Giudicelli Y. In Vivo and in Vitro ob Gene Expression and Leptin Secretion in Rat Adipocytes: Evidence for a Regional Specific Regulation by Sex Steroid Hormones. Endocrinology 1999;140(4): 1567-74.

Chen F, Lee N, Soong Y. Changes in the lipoprotein profile in postmenopausal women receiving hormone replacement therapy. J Reprod Med 1998;43:568.

Cheugn AP. Acuta effects of estradiol and progesterone on insulin, lipids and lipoproteins in postmenopausal women: A pilot study. Maturitas 2000;35:45.

Burger HG, Dudley EC, Hopper JL. The Endocrinology of the menopausal transition: A cross- sectional study of a population – based sample. J Clin Endocrinol Metab 1995;80:3537-40.

Hassager C, Christiansen C. Estragen / Gestagen theraphy changes soft tissue body composition in postmenopausal women. Metabolism 1989;38:662-5.

Martin L, Siliart B, Dumon H, Backus R, Biourge V, Nguyen P. Leptin, body fat content and energy expenditure in intact and gonadectomized adult cats: a preliminary study. J Anim Physiol Anim Nutr 85 2001;85(7-8):195–99.

Houpt KA, Coren B, Hintz HF, Hilderbrant JE. Effect of sex and reproductive status on sucrose preference, food intake, and body weight of dogs. J Am Vet Med Assoc 1979;174:1083–85.

Kimura M, Irahara M, Yasui, T, Saito S, Tezuka M, Yamano. S, Kamada M, Aono T. et al. The obesity in bilateral ovariectomized rats is related to a decrease in the expressionof leptin receptors in the brain. Biochem Biophys Res. Commun 2002;290:1349-53.

Ohkubo T, Tanaka M, Nakashima K. Structure and tissue distribution of chicken leptin receptor (cOb-R) mRNA. Biochim Biophys Acta. 2000;1491:303-308

Fromowitz FB, Viola MV, Chao S, Oravez S, Mishriki Y, Finkel G, Grimson R, Lundy J. Ras 21 expression in the progression of breast cancer. Human Pathology 1987;18:1268-75.

Almey A, Milner TA, Brake WG. Estrogen receptors in the central nervous system and their implication for dopamine-dependent cognition in females. Horm Behav. 2015;74:125–38.

Mcneill AM, Zhang C, Stanczyk, Duckles SP, Krause DN. Estrogen Increases Endothelial Nitric Oxide Synthase via Estrogen Receptors in Rat Cerebral Blood Vessels. Stroke 2002;33:1685-91

Aparicio T, Kermorgant S, Darmoul D, Guilmeau S, Hormi K, Mahieu-Caputo D, Lehy T. Leptin and Ob-Rb receptor ısoform in the human digestive tract during fetal development. J Clin Endocrinol Metab 2005;90(11):6177-6184

FitzGread AJ, Mandir N, Goodlad RA. Leptin, cell proliferation and criypt fission in the gastrointestinal tract of intravenously fed rats. Cell Prolif 2005;38:25-33

Poulsen SS, Nexo E, Olsen PS, Hess J, Kirkegaard P. Immunohistochemical localization of epidermal growth factor in rat and man. Histochemistry 1986;85:389-94

Plaisancie P, Ducroc R, Homsi ME, Tsocas A, Guilmeau S, Zoghbi S, Thibaudeau O, Bado A. Luminal leptin activites mucin-secreting goblet cells in the large bowel. Am J Physiol Gastrointest Liver Physiol 2006;290:805-12.

Homsi ME, Ducroc R., Claustre J, Jourdan G, Gertler A, Estienne M, Bado A, Scoazec JY, Plaisancié P. Leptin modulates the expression of secreted and membrane associated mucins in colonic epithelial cells by targeting PKC, PI3K, and MAPK pathways. Am J Physiol Gastrointest Liver Physiol 2007;293(1) :G365-73.

Thomas ML, XU X, Norfleet AM, Watson CS. The presence of functional estrogen receptrors in intestinal epithelial cells. Endocrinology 1993;132:426-30.

Fernández-Ruiz JJ, Amor, JC, Ramos JA. Time-dependent effects of estradiol and progesterone on the number of striatal dopaminergic D2-receptors. Brain Res.1989; 476:388-95.

Schäfers C, Teigeler M,, Wenzel A, Maack G, Fenske M, Segner H. Concentration- and Time-dependent Effects of the Synthetic Estrogen, 17a-ethinylestradiol, on Reproductive Capabilities of the Zebrafish, Danio rerio. J Toxicol Environ Health A 2007;70(9):768-77.