Effects of obesity in rats on prostate histology and expression of leptin receptor, prolactin receptor, IL-6, and NF-κB

Authors

  • D. Herrera-Covarrubias Universidad Veracruzana
  • C.A. Pérez-León Universidad Veracruzana
  • C. Fernández-Pomares Universidad Veracruzana
  • G.A. Coria-Avila Universidad Veracruzana
  • V. Sánchez-Zavaleta Universidad Veracruzana
  • G.E. Aranda-Abreu Universidad Veracruzana
  • J. Suárez-Medellín Universidad Veracruzana
  • F. Rojas-Durán Universidad Veracruzana
  • M.E. Hernández Universidad Veracruzana

DOI:

https://doi.org/10.32471/exp-oncology.2312-8852.vol-43-no-4.16826

Keywords:

IL-6, leptin, leptin receptor, NF-kB, obesity, prolactin, prolactin receptor, prostate

Abstract

Summary. Background: Hypercaloric intake can lead to obesity, which is a major risk factor associated with chronic subclinical inflammation and many types of cancer. It can increase the serum levels of leptin, prolactin, nuclear factor kappa B (NF-кB) and interleukin (IL)-6, implicated in cell proliferation, differentiation and survival. Aim: To explore the effects of obesity induced by chronic hypercaloric diet in rats on the long-term expression of leptin receptor (OB-R), prolactin receptor, NF-кB, and IL-6, and the changes of histology in rat prostate. Materials and Methods: From postnatal day 21, experimental males were fed with normal chow or chow plus enriched hypercaloric liquid diet. On the postnatal day 90 (13 week old), the animals were euthanized for prostate histology (hematoxylin and eosin staining) and hormone receptors analysis by Western blot. Results: Hypercaloric diet resulted in obesity (32% higher body weight). The prostates of the obese males showed epithelium anisocytosis and compressed interstice. There was also greater volume of lipidic content, anisokaryosis, alterations of the nucleus-cytoplasm ratio, and apparent proplasia. Measures in the ventral prostate (VP) showed that alveoli area increased, but epithelium height and nucleus area were reduced. In the dorsolateral prostate, there was only reduction of nucleus area and presence of mononuclear cells in the lumen. Hypercaloric males also expressed a trend for more OB-R 130 kD in the VP, but no changes were observed with regard to prolactin receptor, NF-кB and IL-6. Conclusion: The obesity due to chronic consumption of hypercaloric diet affects both prostatic regions, but VP is possibly more sensitive via OB-R. We suggest that longer periods of obesity are needed to alter other receptors or the molecular markers of inflammation.

References

Samad N. Serum levels of leptin, zinc and tryptophan with obesity: A case-control study. Pak J Pharm Sci 2017; 30: 1691–6.

Macedo IC, Medeiros LF, Oliveira C, et al. Cafeteria diet-induced obesity plus chronic stress alter serum leptin levels. Peptides 2012; 38: 189–96. https://doi.org/10.1016/j.peptides.2012.08.007

Herrera-Covarrubias, Coria-Avila GA, Fernández-Pomares C, et al. La obesidad como factor de riesgo en el desarrollo de cáncer. Rev Peru Med Exp Salud Publica 2015; 32: 766–76.

Colli S, Cavalcante FS, Martins MP, et al. Leptin role in the rat prostate ventral lobe. Fertil Steril 2011; 95: 1490–3.e1. doi:S0015-0282 (10)02971-7 [pii]10.1016/ j.fertnstert.2010.12.029

Garofalo C, Surmacz E. Leptin and cancer. J Cell Physiol 2006; 207: 12–22. https://doi.org/10.1002/jcp.20472

Greenman Y, Tordjman K, Stern N. Increased body weight associated with prolactin secreting pituitary adenomas: weight loss with normalization of prolactin levels. Clin Endocrinol (Oxf) 1998; 48: 547–53. https://doi.org/10.1046/j.1365-2265.1998.00403.x

Gala RR. The physiology and mechanisms of the stress-induced changes in prolactin secretion in the rat. Life Sci 1990; 46: 1407–20. https://doi.org/10.1016/0024-3205(90)90456-2

Pascual-Mathey LI, Rojas-Duran F, Aranda-Abreu GE, et al. Effect of hyperprolactinemia on PRL-receptor expression and activation of Stat and Mapk cell signaling in the prostate of long-term sexually-active rats. Physiol Behav 2016; 157: 170–7. https://doi.org/10.1016/j.physbeh.2016.02.011

Freeman M, Kanyicska B, Lerant A, et al. Prolactin: Structure, Function, and Regulation of Secretion. Physiol Rev 2000; 80: 1523–31. https://doi.org/10.1152/physrev.2000.80.4.1523

Herrera-Covarrubias D, Coria-Avila GA, Chavarria-Xicotencatl P, et al. Long-term administration of prolactin or testosterone induced similar precancerous prostate lesions in rats. Exp Oncol 2015; 37: 13–18.

Herrera-Covarrubias D, Coria-Avila GA, Aranda-Abreu GE, et al. Prepuberal stress and obesity: effects on serum corticosterone, prolactin, testosterone and precancerous prostate lesions in adult rats. Exp Oncol 2019; 41: 130–7. https://doi.org/10.32471/exp-oncology.2312-8852.vol-41-no-2.13093

Ajuwon KM, Spurlock ME. Adiponectin inhibits LPS-induced NF-kappaB activation and IL-6 production and increases PPARgamma2 expression in adipocytes. Am J Physiol Regul Integr Comp Physiol 2005; 288: R1220–5. https://doi.org/10.1152/ajpregu.00397.2004

Kim F, Pham M, Luttrell I, et al. Toll-like receptor-4 mediates vascular inflammation and insulin resistance in diet-induced obesity. Circ Res 2007; 100: 1589–96. https://doi.org/10.1161/CIRCRESAHA.106.142851

Herrera-Covarrubias D, Coria-Avila G, Hernandez ME, et al. Stress during puberty facilitates precancerous prostate lesions in adult rats. Exp Oncol 2017; 39: 269–75.

Goldman A, Harper S, Speicher D. Detection of proteins on blot membranes. Curr Protoc Protein Sci 2016; 86: 10.8.1-10.8.11. https://doi.org/10.1002/cpps.15

Haque R, Van Den Eeden SK, Wallner LP, et al. Association of body mass index and prostate cancer mortality. Obes Res Clin Pract 2014; 8: e374–81. https://doi.org/10.1016/j.orcp.2013.06.002

Hales CM, Carroll MD, Fryar CD, et al. Prevalence of obesity and severe obesity among adults: United States, 2017–2018. In NCHS Data Brief. 2020, National Center For Health Statistics: Hyattsville, MD: 1–8.

Chang SN, Han J, Abdelkader TS, et al. High animal fat intake enhances prostate cancer progression and reduces glutathione peroxidase 3 expression in early stages of TRAMP mice. Prostate 2014; 74: 1266–77. https://doi.org/10.1002/pros.22843

Grassi TF, Bidinotto LTL, Lopes GAD, et al. Maternal western-style diet enhances the effects of chemically-induced mammary tumors in female rat offspring through transcriptome changes. Nutr Res 2019; 61: 41–52. https://doi.org/10.1016/j.nutres.2018.09.009

Downloads

Published

26.05.2023

How to Cite

Herrera-Covarrubias, D., Pérez-León, C., Fernández-Pomares, C., Coria-Avila, G., Sánchez-Zavaleta, V., Aranda-Abreu, G., … Hernández, M. (2023). Effects of obesity in rats on prostate histology and expression of leptin receptor, prolactin receptor, IL-6, and NF-κB. Experimental Oncology, 43(4), 317–321. https://doi.org/10.32471/exp-oncology.2312-8852.vol-43-no-4.16826

Issue

Section

Original contributions