Skip to content
2000
Volume 32, Issue 1
  • ISSN: 0929-8665
  • E-ISSN: 1875-5305

Abstract

Background

Cholelithiasis is the most prevalent inflammatory condition of the gallbladder. The regulation of biological processes, including energy homeostasis, and control of body weight are key mechanisms that the leptin and melanocortin pathways play a role in Cholelithiasis is the most prevalent inflammatory condition of the gallbladder. There are various risk factors for the development of gallstone disease, especially weight gain, and obesity is just one of them. This risk factor can be minimized by maintaining appetite and energy balance. Here, leptin and melanocortin pathways are the key mechanisms in maintaining appetite and energy homeostasis.

Objectives

The aim of this study was to investigate the relationship between the levels of LEP, LEPR, TrkB, BDNF, POMC, and MC4R proteins in patients with Cholelithiasis. This study aims to determine the relationship between LEP, LEPR, TrkB, BDNF, POMC, and MC4R protein levels, which play a role in maintaining appetite and energy homeostasis, and cholelithiasis.

Methods

This study examined 44 patients diagnosed with Cholelithiasis and 44 healthy control subjects who had not previously been diagnosed with any form of Cholelithiasis. The levels of leptin (LEP), Leptin Binds To Leptin Receptors (LEPR), Tropomyosin Receptor Kinase B (TrkB), Brain-Derived Neurotrophic Factor (BDNF), Pro-OpioMelanoCortin (POMC), and Melanocortin-4 Receptors (MC4R) molecules were analyzed using the Enzyme-Linked Immunosorbent Assay (ELISA) method. The results were analyzed using the SPSS Software (Version 22.0) program and GraphPad Prism 8.0.1 software.

Results

The study found a statistically significant decrease ( < 0.05) in MC4R, TrkB, BDNF, and POMC protein levels in Cholelithiasis patients compared to the control group. There was no statistically significant difference in LEP and LEPR concentration values between the two groups ( = 0.247, = 0.674).

Conclusion

The proteins MC4R, TrkB, BDNF, and POMC, which are involved in the leptin and melanocortin pathways may play a significant role in Cholelithiasis disease. However, more detailed research on the relevant proteins is needed. Nevertheless, this research will guide new studies.

Loading

Article metrics loading...

/content/journals/ppl/10.2174/0109298665343979241025114114
2024-11-22
2025-06-28
Loading full text...

Full text loading...

References

  1. EverhartJ.E. RuhlC.E. Burden of digestive diseases in the United States Part III: Liver, biliary tract, and pancreas.Gastroenterology200913641134114410.1053/j.gastro.2009.02.03819245868
    [Google Scholar]
  2. TazumaS. Epidemiology, pathogenesis, and classification of biliary stones (common bile duct and intrahepatic).Best Pract. Res. Clin. Gastroenterol.20062061075108310.1016/j.bpg.2006.05.00917127189
    [Google Scholar]
  3. DiehlA.K. RosenthalM. HazudaH.P. ComeauxP.J. SternM.P. Socioeconomic status and the prevalence of clinical gallbladder disease.J. Chronic Dis.198538121019102610.1016/0021‑9681(85)90100‑63877735
    [Google Scholar]
  4. FreemanJ. BoomerL. FursevichD. FelizA. Ethnicity and insurance status affect health disparities in patients with gallstone disease.J. Surg. Res.201217511510.1016/j.jss.2011.06.06421872888
    [Google Scholar]
  5. 5 Centers for Disease Control and Prevention (CDC). Vital signs: State-specific obesity prevalence among adults - United States, 2009.MMWR Morb. Mortal. Wkly. Rep.201059951955
    [Google Scholar]
  6. LoriaP. LonardoA. LombardiniS. CarulliL. VerroneA. GanazziD. RudilossoA. D’AmicoR. BertolottiM. CarulliN. Gallstone disease in non-alcoholic fatty liver: Prevalence and associated factors.J. Gastroenterol. Hepatol.20052081176118410.1111/j.1440‑1746.2005.03924.x16048564
    [Google Scholar]
  7. ChangY. SungE. RyuS. ParkY.W. JangY.M. ParkM. Insulin resistance is associated with gallstones even in non-obese, non-diabetic Korean men.J. Korean Med. Sci.200823464465010.3346/jkms.2008.23.4.64418756051
    [Google Scholar]
  8. SchwartzM.W. WoodsS.C. PorteD.Jr SeeleyR.J. BaskinD.G. Central nervous system control of food intake.Nature2000404677866167110.1038/3500753410766253
    [Google Scholar]
  9. ZhangY. ProencaR. MaffeiM. BaroneM. LeopoldL. FriedmanJ.M. Positional cloning of the mouse obese gene and its human homologue.Nature1994372650542543210.1038/372425a07984236
    [Google Scholar]
  10. LiuZ. XiaoT. LiuH. Leptin signaling and its central role in energy homeostasis.Front. Neurosci.202317123852810.3389/fnins.2023.123852838027481
    [Google Scholar]
  11. ObradovicM. Sudar-MilovanovicE. SoskicS. EssackM. AryaS. StewartA.J. GojoboriT. IsenovicE.R. Leptin and obesity: Role and clinical implication.Front. Endocrinol. (Lausanne)20211258588710.3389/fendo.2021.58588734084149
    [Google Scholar]
  12. MargeticS GazzolaC PeggGG HillRA Leptin: A review of its peripheral actions and interactions.Int. J. Obes. Relat. Metab. Disord.200226111407143310.1038/sj.ijo.0802142
    [Google Scholar]
  13. FrederichR.C. HamannA. AndersonS. LöllmannB. LowellB.B. FlierJ.S. Leptin levels reflect body lipid content in mice: Evidence for diet-induced resistance to leptin action.Nat. Med.19951121311131410.1038/nm1295‑13117489415
    [Google Scholar]
  14. MaffeiM. HalaasJ. RavussinE. PratleyR.E. LeeG.H. ZhangY. FeiH. KimS. LalloneR. RanganathanS. KernP.A. FriedmanJ.M. Leptin levels in human and rodent: Measurement of plasma leptin and ob RNA in obese and weight-reduced subjects.Nat. Med.19951111155116110.1038/nm1195‑11557584987
    [Google Scholar]
  15. GautronL. ElmquistJ.K. Sixteen years and counting: An update on leptin in energy balance.J. Clin. Invest.201112162087209310.1172/JCI4588821633176
    [Google Scholar]
  16. ElmquistJ.K. BjørbaekC. AhimaR.S. FlierJ.S. SaperC.B. Distributions of leptin receptor mRNA isoforms in the rat brain.J. Comp. Neurol.1998395453554710.1002/(SICI)1096‑9861(19980615)395:4<535::AID‑CNE9>3.0.CO;2‑29619505
    [Google Scholar]
  17. ScottM.M. LacheyJ.L. SternsonS.M. LeeC.E. EliasC.F. FriedmanJ.M. ElmquistJ.K. Leptin targets in the mouse brain.J. Comp. Neurol.2009514551853210.1002/cne.2202519350671
    [Google Scholar]
  18. SchwartzM.W. SeeleyR.J. CampfieldL.A. BurnP. BaskinD.G. Identification of targets of leptin action in rat hypothalamus.J. Clin. Invest.19969851101110610.1172/JCI1188918787671
    [Google Scholar]
  19. TartagliaL.A. DembskiM. WengX. DengN. CulpepperJ. DevosR. RichardsG.J. CampfieldL.A. ClarkF.T. DeedsJ. MuirC. SankerS. MoriartyA. MooreK.J. SmutkoJ.S. MaysG.G. WoolE.A. MonroeC.A. TepperR.I. Identification and expression cloning of a leptin receptor, OB-R.Cell19958371263127110.1016/0092‑8674(95)90151‑58548812
    [Google Scholar]
  20. FeiH. OkanoH.J. LiC. LeeG.H. ZhaoC. DarnellR. FriedmanJ.M. Anatomic localization of alternatively spliced leptin receptors (Ob-R) in mouse brain and other tissues.Proc. Natl. Acad. Sci. USA199794137001700510.1073/pnas.94.13.70019192681
    [Google Scholar]
  21. MoranO. PhillipM. Leptin: Obesity, diabetes and other peripheral effects - a review.Pediatr. Diabetes20034210110910.1034/j.1399‑5448.2003.00017.x14655266
    [Google Scholar]
  22. GarofaloC. SurmaczE. Leptin and cancer.J. Cell. Physiol.20062071122210.1002/jcp.2047216110483
    [Google Scholar]
  23. KošutaI. MrzljakA. KolarićB. VučićL.M. M. Vucic Lovrencic Leptin as a key player in insulin resistance of liver cirrhosis? A cross-sectional study in liver transplant candidates.J. Clin. Med.20209256010.3390/jcm902056032092909
    [Google Scholar]
  24. Martínez-UñaM. López-MancheñoY. DiéguezC. Fernández-RojoM.A. NovelleM.G. Unraveling the role of leptin in liver function and its relationship with liver diseases.Int. J. Mol. Sci.20202124936810.3390/ijms2124936833316927
    [Google Scholar]
  25. FloreaniA. VariolaA. NiroG. PremoliA. BaldoV. GambinoR. MussoG. CassaderM. BoS. FerraraF. CaroliD. RizzottoE.R. DurazzoM. Plasma adiponectin levels in primary biliary cirrhosis: A novel perspective for link between hypercholesterolemia and protection against atherosclerosis.Am. J. Gastroenterol.200810381959196510.1111/j.1572‑0241.2008.01888.x18564121
    [Google Scholar]
  26. GoitR.K. TaylorA.W. LoA.C.Y. The central melanocortin system as a treatment target for obesity and diabetes: A brief overview.Eur. J. Pharmacol.202292417495610.1016/j.ejphar.2022.17495635430211
    [Google Scholar]
  27. ShafferE.A. Epidemiology and risk factors for gallstone disease: Has the paradigm changed in the 21st century?Curr. Gastroenterol. Rep.20057213214010.1007/s11894‑005‑0051‑815802102
    [Google Scholar]
  28. ItoE. IhaK. YoshimuraT. NakaishiK. WatabeS. Early diagnosis with ultrasensitive ELISA.Adv. Clin. Chem.202110112113310.1016/bs.acc.2020.06.00233706887
    [Google Scholar]
  29. PengP. LiuC. LiZ. XueZ. MaoP. HuJ. XuF. YaoC. YouM. Emerging ELISA derived technologies for in vitro diagnostics.Trends Analyt. Chem.202215211660510.1016/j.trac.2022.116605
    [Google Scholar]
  30. FranciscoV. PinoJ. Campos-CabaleiroV. Ruiz-FernándezC. MeraA. Gonzalez-GayM.A. GómezR. GualilloO. O. GualilloObesity, fat mass and immune system: Role for leptin.Front. Physiol.2018964010.3389/fphys.2018.0064029910742
    [Google Scholar]
  31. VoumvourakiA. KoulentakiM. NotasG. SfakianakiO. KouroumalisE. Serum surrogate markers of liver fibrosis in primary biliary cirrhosis.Eur. J. Intern. Med.2011221778310.1016/j.ejim.2010.10.00221238899
    [Google Scholar]
  32. SzalayF. FolhofferA. HorváthA. CsakT. SpeerG. NagyZ. LakatosP. HorváthC. HabiorA. TornaiI. LakatosP.L. Serum leptin, soluble leptin receptor, free leptin index and bone mineral density in patients with primary biliary cirrhosis.Eur. J. Gastroenterol. Hepatol.200517992392810.1097/00042737‑200509000‑0000716093869
    [Google Scholar]
  33. Ben-AriZ. SchaferZ. SulkesJ. ManhaimV. Tur-KaspaR. FainaruM. Alterations in serum leptin in chronic liver disease.Dig. Dis. Sci.200247118318910.1023/A:101324842778311837722
    [Google Scholar]
  34. OweckiM. NikischE. MiczkeA. Pupek-MusialikD. SowińskiJ. Leptin, soluble leptin receptors, free leptin index, and their relationship with insulin resistance and BMI: High normal BMI is the threshold for serum leptin increase in humans.Horm. Metab. Res.201042858558910.1055/s‑0030‑125342220455195
    [Google Scholar]
  35. SéronK. CorsetL. VasseurF. BoutinP. Gómez-AmbrosiJ. SalvadorJ. FrühbeckG. FroguelP. Distinct impaired regulation of SOCS3 and long and short isoforms of the leptin receptor in visceral and subcutaneous fat of lean and obese women.Biochem. Biophys. Res. Commun.200634841232123810.1016/j.bbrc.2006.07.06816920065
    [Google Scholar]
  36. BurnsB. SchmidtK. WilliamsS.R. KimS. GirirajanS. ElseaS.H. Rai1 haploinsufficiency causes reduced Bdnf expression resulting in hyperphagia, obesity and altered fat distribution in mice and humans with no evidence of metabolic syndrome.Hum. Mol. Genet.201019204026404210.1093/hmg/ddq31720663924
    [Google Scholar]
  37. TsaoD. ThomsenH.K. ChouJ. StrattonJ. HagenM. LooC. GarciaC. SloaneD.L. RosenthalA. LinJ.C. TrkB agonists ameliorate obesity and associated metabolic conditions in mice.Endocrinology200814931038104810.1210/en.2007‑116618063676
    [Google Scholar]
  38. Kawamoto, M.; Ozono, K.; Oyama, Y.; Yamasaki, A.; Oda, Y.; Onishi, H. The novel selective Pan-TRK inhibitor ONO-7579 exhibits antitumor efficacy against human gallbladder cancer in vitro Anticancer Res.2018384197986
    [Google Scholar]
  39. YeoG.S.H. Connie HungC.C. RochfordJ. KeoghJ. GrayJ. SivaramakrishnanS. O’RahillyS. FarooqiI.S. A de novo mutation affecting human TrkB associated with severe obesity and developmental delay.Nat. Neurosci.20047111187118910.1038/nn133615494731
    [Google Scholar]
  40. XiongL. DengX. WenY. YangZ. MiaoX. Association of BDNF and BMPR1A with clinicopathologic parameters in benign and malignant gallbladder lesions.World J. Surg. Oncol.20131118010.1186/1477‑7819‑11‑8023531103
    [Google Scholar]
  41. KawamotoM. OnishiH. OzonoK. YamasakiA. ImaizumiA. NakamuraM. TrkB/BDNF signaling promotes EMT mediated invasiveness and is a potential therapeutic target for gallbladder cancer.Ann. Oncol.201627vi23610.1093/annonc/mdw371.93
    [Google Scholar]
  42. de SouzaF.S.J. SantangeloA.M. BumaschnyV. AvaleM.E. SmartJ.L. LowM.J. RubinsteinM. Identification of neuronal enhancers of the proopiomelanocortin gene by transgenic mouse analysis and phylogenetic footprinting.Mol. Cell. Biol.20052583076308610.1128/MCB.25.8.3076‑3086.200515798195
    [Google Scholar]
  43. ZhouS. ChenW. BaiX. ChenJ. XuQ. DongL. ChenW. QuQ. HeX. Upregulation of hypothalamic POMC neurons after biliary diversion in GK rats.Front. Endocrinol. (Lausanne)20221399992810.3389/fendo.2022.99992836277690
    [Google Scholar]
  44. Nf-kappaB. The anti-metastatic potential of POMC gene transfer in melanoma.Mol. Ther.2008161
    [Google Scholar]
  45. FaccioliN. PoitouC. ClémentK. DubernB. Current treatments for patients with genetic obesity.J. Clin. Res. Pediatr. Endocrinol.202315210811910.4274/jcrpe.galenos.2023.2023‑3‑237191347
    [Google Scholar]
  46. ShabanzadehD.M. SkaabyT. SørensenL.T. Eugen-OlsenJ. JørgensenT. Metabolic biomarkers and gallstone disease – a population-based study.Scand. J. Gastroenterol.201752111270127710.1080/00365521.2017.136516628799434
    [Google Scholar]
  47. YeoG.S.H. ChaoD.H.M. SiegertA.M. KoerperichZ.M. EricsonM.D. SimondsS.E. LarsonC.M. LuquetS. ClarkeI. SharmaS. ClémentK. CowleyM.A. Haskell-LuevanoC. Van Der PloegL. AdanR.A.H. The melanocortin pathway and energy homeostasis: From discovery to obesity therapy.Mol. Metab.20214810120610.1016/j.molmet.2021.10120633684608
    [Google Scholar]
  48. BaldiniG. PhelanK.D. The melanocortin pathway and control of appetite-progress and therapeutic implications.J. Endocrinol.20192411R1R3310.1530/JOE‑18‑059630812013
    [Google Scholar]
/content/journals/ppl/10.2174/0109298665343979241025114114
Loading
/content/journals/ppl/10.2174/0109298665343979241025114114
Loading

Data & Media loading...


  • Article Type:
    Research Article
Keyword(s): BDNF; Cholelithiasis; LEP; LEPR; leptin-melanocortin pathway; MC4R; POMC; TrkB
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test