Influence of vagus nerve and spleen ablation on brown adipose tissue histology of hypothalamic obese and non-obese male Wistar rats
Main Article Content
Abstract
Vagus nerve and spleen can influence metabolic function and adiposity. Brown adipose tissue is an organ specialized in thermogenesis, a biochemistry process of lipids degradation that results in heat production, elevating energy expenditure and contributing to anti-obesity effects.
Aim: Here, we evaluated the impact of vagus nerve and spleen absence on histology and lipid deposition of brown adipose tissue from non-obese and hypothalamic obese male Wistar rats.
Methods: Hypothalamic obesity was induced by neonatal glutamate L-monosodium (4g/Kg) administration during the first post-natal days. Control rats received equimolar saline. At 60 days of life, obese and control groups underwent surgery: vagotomy, splenectomy, and sham. At 150 days of life, the animals were weighed and measured. Blood was collected for biochemistry analysis of glucose and triglycerides, and insulin resistance evaluated. Moreover, white adipose tissue and brown adipose tissue depots were removed and weighed. Brown adipose tissue was histologically analyzed.
Results: In obese animals, elevated adiposity, hypertriglyceridemia, insulin resistance and higher lipid deposition in brown adipose tissue were noted. Vagus nerve ablation displayed more pronounced anti-adiposity effects, improving triglyceride plasma levels and insulin resistance in the obese rats compared to the control group. Moreover, spleen absence, especially in the obese group, raises nuclei number and reduced adipocyte size. These responses were amplified by vagus nerve ablation.
Conclusion: Hypothalamic obese rats show excessive adiposity and metabolic dysfunctions related to brown adipose tissue hypofunction. Vagus nerve and spleen absence reduced lipid deposition on brown adipose tissue of obese rats, suggesting reactivation of thermogenesis.
Keywords:
brown adipocytes; obesity; vagal dysfunction; splenic tissue.
Article Details
How to Cite
NOTTAR, Cassiane Lisbinski et al.
Influence of vagus nerve and spleen ablation on brown adipose tissue histology of hypothalamic obese and non-obese male Wistar rats.
Medical Research Archives, [S.l.], v. 12, n. 11, nov. 2024.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6009>. Date accessed: 12 dec. 2024.
doi: https://doi.org/10.18103/mra.v12i11.6009.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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2. Corrêa, Heyn, Magalhaes. The Impact of the Adipose Organ Plasticity on Inflammation and Cancer Progression. Cells. 2019;8(7):662. doi:10.3390/cell s8070662
3. Fonseca-Alaniz MH, Takada J, Alonso-Vale MIC, Lima FB. The adipose tissue as a regulatory center of the metabolism. Arq Bras Endocrinol Metabol. 2006;50(2):216-229. doi:10.1590/s0004-27302006 000200008
4. Mariath AB, Grillo LP, Silva RO da, et al. Obesity and risk factors for the development of chronic non-transmissible diseases among consumers in a foodservice unit. Cad Saude Publica. 2007;23 (4):897-905. doi:10.1590/s0102-311x2007000400017
5. Worku MG, Seretew WS, Angaw DA, Tesema GA. Prevalence and Associated Factor of Brown Adipose Tissue: Systematic Review and Meta-Analysis. BioMed Res Int. 2020;2020:9106976. doi:10.115 5/2020/9106976
6. Boschini RP, Garcia Júnior JR. Regulação da expressão gênica das UCP2 e UCP3 pela restrição energética, jejum e exercício físico. Rev Nutr. 2005;18(6):753-764. doi:10.1590/S1415-52732005 000600006
7. Francine Naiara Broetto, Maria do Nascimento Brito. Tecido adiposo marrom e obesidade em humanos. Rev Saúde E Pesqui. 2012;5(1):121-135.
8. Porter C. Quantification of UCP1 function in human brown adipose tissue. Adipocyte. 2017;6 (2):167-174. doi:10.1080/21623945.2017.1319535
9. Adilson Domingos dos Reis Filho, Roberto Carlos Vieira Junior, Fabrício Azevedo Voltarelli. Exercicio fisico, proteina desacopladora-3 e termogenese. Rev Bras Prescrição E Fisiol Exerc. 2013;7(38):176-183.
10. Depieri TZ, Pinto RR, Catarin JK, de Carli MCL, Garcia Júnior JR. UCP-3: regulation of genic expression on skeletal muscle and possible role on body weight control. Arq Bras Endocrinol Metabol. 2004;48(3):337-344. doi:10.1590/s0004-27302004 000300003
11. Vijgen GHEJ, Bouvy ND, Leenen L, et al. Vagus nerve stimulation increases energy expenditure: relation to brown adipose tissue activity. PloS One. 2013;8(10):e77221. doi:10.1371/journal.pone.0077221
12. Liu C, Bookout AL, Lee S, Sun K, Jia L, Lee C, Udit S, Deng Y, Scherer PE, Mangelsdorf DJ, Gautron L, Elmquist JK. PPARγ in vagal neurons regulates high-fat diet induced thermogenesis. Cell Metab. 2014 Apr 1;19(4):722-30. doi: 10.1016/j.cmet.201 4.01.021. PMID: 24703703; PMCID: PMC4046333.
13. Lee HC, Curry DL, Stern JS. Direct effect of CNS on insulin hypersecretion in obese Zucker rats: involvement of vagus nerve. Am J Physiol. 1989 Mar;256(3 Pt 1):E439-44. doi: 10.1152/ajpendo.19 89.256.3.E439. PMID: 2646948.
14. Balbo SL, Grassiolli S, Ribeiro RA, Bonfleur ML, Gravena C, Brito Mdo N, Andreazzi AE, Mathias PC, Torrezan R. Fat storage is partially dependent on vagal activity and insulin secretion of hypothalamic obese rat. Endocrine. 2007 Apr;31(2):142-8. doi: 10.1007/s12020-007-0021-z. PMID: 17873325.
15. Barella LF, Miranda RA, Franco CC, Alves VS, Malta A, Ribeiro TA, Gravena C, Mathias PC, de Oliveira JC. Vagus nerve contributes to metabolic syndrome in high-fat diet-fed young and adult rats. Exp Physiol. 2015 Jan;100(1):57-68. doi: 10.1113/e xpphysiol.2014.082982. Epub 2014 Dec 18. PMID: 25398717.
16. Catinis AM, Hinojosa AJ, Leonardi C, Cook MW. Hepatic Vagotomy in Patients With Obesity Leads to Improvement of the Cholesterol to High-Density Lipoprotein Ratio. Obes Surg. 2023 Dec; 33(12):3740-3745. doi: 10.1007/s11695-023-0680 0-2. Epub 2023 Nov 4. PMID: 37924466.
17. Lubaczeuski C, Balbo SL, Ribeiro RA, et al (2015) Vagotomy ameliorates islet morphofunction and body metabolic homeostasis in MSG-obese rats. Brazilian Journal of Medical and Biological
Research 48:447–457. https://doi.org/10.1590/1414-431X20144340
18. Székely M. The vagus nerve in thermoregulation and energy metabolism. Auton Neurosci Basic Clin. 2000;85(1-3):26-38. doi:10.1016/S1566-0702(00)00217-4
19. Hibi M, Oishi S, Matsushita M, et al. Brown adipose tissue is involved in diet-induced thermogenesis and whole-body fat utilization in healthy humans. Int J Obes 2005. 2016;40(11): 1655-1661. doi:10.1038/ijo.2016.124
20. Yamazaki T, Morimoto-Kobayashi Y, Koizumi K, Takahashi C, Nakajima S, Kitao S, et al.. Secretion of a gastrointestinal hormone, cholecystokinin, by hop-derived bitter components activates sympathetic nerves in brown adipose tissue. J Nutr Biochem. (2019) 64:80–7. 10.1016/j.j nutbio.2018.10.009
21. Saito M, Matsushita M, Yoneshiro T, Okamatsu-Ogura Y. Brown Adipose Tissue, Diet-Induced Thermogenesis, and Thermogenic Food Ingredients: From Mice to Men. Front Endocrinol. 2020;11:222. doi:10.3389/fendo.2020.00222
22. Mano-Otagiri A, Iwasaki-Sekino A, Nemoto T, et al. Genetic suppression of ghrelin receptors activates brown adipocyte function and decreases fat storage in rats. Regul Pept. 2010;160(1-3):81-90. doi:10.1016/j.regpep.2009.11.010
23. Matteoli G, Gomez-Pinilla PJ, Nemethova A, et al. A distinct vagal anti-inflammatory pathway modulates intestinal muscularis resident macrophages independent of the spleen. Gut. 2014;63(6):938-948. doi:10.1136/gutjnl-2013-304676
24. Tarantino G, Scalera A, Finelli C. Liver-spleen axis: intersection between immunity, infections and metabolism. World J Gastroenterol. 2013;19(23): 3534-3542. doi:10.3748/wjg.v19.i23.3534
25. Knoll M, Winther S, Natarajan A, et al. SYK kinase mediates brown fat differentiation and activation. Nat Commun. 2017;8(1):2115. doi:10.1038/s41467-017-02162-3
26. Olney JW. Brain lesions, obesity, and other disturbances in mice treated with monosodium glutamate. Science. 1969;164(3880):719-721. doi:10.1126/science.164.3880.719
27. Gotoh K, Inoue M, Shiraishi K, et al. Spleen-derived interleukin-10 downregulates the severity of high-fat diet-induced non-alcoholic fatty pancreas disease. PloS One. 2012;7(12):e53154.
doi:10.1371/journal.pone.0053154
28. Simental-Mendía LE, Rodríguez-Morán M, Guerrero-Romero F (2008) The product of fasting glucose and triglycerides as surrogate for identifying insulin resistance in apparently healthy subjects. Metab Syndr Relat Disord 6:299–304. https://doi.org/10.1089/met.2008.0034
29. Bernardis LL, Patterson BD (1968) Correlation Between “Lee Index” And Carcass Fat Content In Weanling And Adult Female Rats With Hypothalamic Lesions. Journal of Endocrinology 40:527–528. https://doi.org/10.1677/joe.0.0400527
30. Konrad S, Farah V, Rodrigues B, et al. Monosodium glutamate neonatal treatment induces cardiovascular autonomic function changes in rodents. Clinics. 2012;67(10):1209-1214. doi:10.6061/clinic s/2012(10)14
31. Voltera AF, Cesaretti MLR, Ginoza M, Kohlmann O. Effects of neuroendocrine obesity induction on systemic hemodynamics and left ventricular function of normotensive rats. Arq Bras Endocrinol Metabol. 2008;52(1):47-54. doi:10.1590/s0004-27302008000100008
32. Corder R, Saudan P, Mazlan M, McLean C, Gaillard RC. Depletion of Hypothalamic Growth Hormone-Releasing Hormone by Neonatal Monosodium Glutamate Treatment Reveals an Inhibitory Effect of Betamethasone on Growth Hormone Secretion in Adult Rats. Neuroendocrinology. 1990;51(1):85-92. doi:10.1159/000125321
33. Nishimoto Y, Tamori Y. CIDE Family-Mediated Unique Lipid Droplet Morphology in White Adipose Tissue and Brown Adipose Tissue Determines the Adipocyte Energy Metabolism. J Atheroscler Thromb. 2017;24(10):989-998. doi:10.5551/jat.RV17011
34. Virtue S, Vidal-Puig A (2013) Assessment of brown adipose tissue function. Front Physiol 4:. https://doi.org/10.3389/fphys.2013.00128
35. Chait A, den Hartigh LJ. Adipose Tissue Distribution, Inflammation and Its Metabolic Consequences, Including Diabetes and Cardiovascular Disease. Front Cardiovasc Med. 2020;7:22.
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