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image of Leptin/Melanocortin Pathway in Cholelithiasis Patients: A Diagnostic Perspective?

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 MC4P 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 (p < 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 (p=0.247, p=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.

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2024-11-22
2025-01-31

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References

  1. Everhart J.E. Ruhl C.E. Burden of digestive diseases in the United States Part III: Liver, biliary tract, and pancreas. Gastroenterology 2009 136 4 1134 1144 10.1053/j.gastro.2009.02.038 19245868
    [Google Scholar]
  2. Tazuma S. Epidemiology, pathogenesis, and classification of biliary stones (common bile duct and intrahepatic). Best Pract. Res. Clin. Gastroenterol. 2006 20 6 1075 1083 10.1016/j.bpg.2006.05.009 17127189
    [Google Scholar]
  3. Diehl A.K. Rosenthal M. Hazuda H.P. Comeaux P.J. Stern M.P. Socioeconomic status and the prevalence of clinical gallbladder disease. J. Chronic Dis. 1985 38 12 1019 1026 10.1016/0021‑9681(85)90100‑6 3877735
    [Google Scholar]
  4. Freeman J. Boomer L. Fursevich D. Feliz A. Ethnicity and insurance status affect health disparities in patients with gallstone disease. J. Surg. Res. 2012 175 1 1 5 10.1016/j.jss.2011.06.064 21872888
    [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. 2010 59 951 955
    [Google Scholar]
  6. Loria P. Lonardo A. Lombardini S. Carulli L. Verrone A. Ganazzi D. Rudilosso A. D’Amico R. Bertolotti M. Carulli N. Gallstone disease in non‐alcoholic fatty liver: Prevalence and associated factors. J. Gastroenterol. Hepatol. 2005 20 8 1176 1184 10.1111/j.1440‑1746.2005.03924.x 16048564
    [Google Scholar]
  7. Chang Y. Sung E. Ryu S. Park Y.W. Jang Y.M. Park M. Insulin resistance is associated with gallstones even in non-obese, non-diabetic Korean men. J. Korean Med. Sci. 2008 23 4 644 650 10.3346/jkms.2008.23.4.644 18756051
    [Google Scholar]
  8. Schwartz M.W. Woods S.C. Porte D. Jr Seeley R.J. Baskin D.G. Central nervous system control of food intake. Nature 2000 404 6778 661 671 10.1038/35007534 10766253
    [Google Scholar]
  9. Zhang Y. Proenca R. Maffei M. Barone M. Leopold L. Friedman J.M. Positional cloning of the mouse obese gene and its human homologue. Nature 1994 372 6505 425 432 10.1038/372425a0 7984236
    [Google Scholar]
  10. Liu Z. Xiao T. Liu H. Leptin signaling and its central role in energy homeostasis. Front. Neurosci. 2023 17 1238528 10.3389/fnins.2023.1238528 38027481
    [Google Scholar]
  11. Obradovic M. Sudar-Milovanovic E. Soskic S. Essack M. Arya S. Stewart A.J. Gojobori T. Isenovic E.R. Leptin and obesity: Role and clinical implication. Front. Endocrinol. (Lausanne) 2021 12 585887 10.3389/fendo.2021.585887 34084149
    [Google Scholar]
  12. Margetic S Gazzola C Pegg GG Hill RA Leptin: A review of its peripheral actions and interactions. Int J Obes Relat Metab Disord. 2002 26 11 1407 1433 10.1038/sj.ijo.0802142
    [Google Scholar]
  13. Frederich R.C. Hamann A. Anderson S. Löllmann B. Lowell B.B. Flier J.S. Leptin levels reflect body lipid content in mice: Evidence for diet-induced resistance to leptin action. Nat. Med. 1995 1 12 1311 1314 10.1038/nm1295‑1311 7489415
    [Google Scholar]
  14. Maffei M. Halaas J. Ravussin E. Pratley R.E. Lee G.H. Zhang Y. Fei H. Kim S. Lallone R. Ranganathan S. Kern P.A. Friedman J.M. Leptin levels in human and rodent: Measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat. Med. 1995 1 11 1155 1161 10.1038/nm1195‑1155 7584987
    [Google Scholar]
  15. Gautron L. Elmquist J.K. Sixteen years and counting: An update on leptin in energy balance. J. Clin. Invest. 2011 121 6 2087 2093 10.1172/JCI45888 21633176
    [Google Scholar]
  16. Elmquist J.K. Bjørbaek C. Ahima R.S. Flier J.S. Saper C.B. Distributions of leptin receptor mRNA isoforms in the rat brain. J. Comp. Neurol. 1998 395 4 535 547 10.1002/(SICI)1096‑9861(19980615)395:4<535::AID‑CNE9>3.0.CO;2‑2 9619505
    [Google Scholar]
  17. Scott M.M. Lachey J.L. Sternson S.M. Lee C.E. Elias C.F. Friedman J.M. Elmquist J.K. Leptin targets in the mouse brain. J. Comp. Neurol. 2009 514 5 518 532 10.1002/cne.22025 19350671
    [Google Scholar]
  18. Schwartz M.W. Seeley R.J. Campfield L.A. Burn P. Baskin D.G. Identification of targets of leptin action in rat hypothalamus. J. Clin. Invest. 1996 98 5 1101 1106 10.1172/JCI118891 8787671
    [Google Scholar]
  19. Tartaglia L.A. Dembski M. Weng X. Deng N. Culpepper J. Devos R. Richards G.J. Campfield L.A. Clark F.T. Deeds J. Muir C. Sanker S. Moriarty A. Moore K.J. Smutko J.S. Mays G.G. Wool E.A. Monroe C.A. Tepper R.I. Identification and expression cloning of a leptin receptor, OB-R. Cell 1995 83 7 1263 1271 10.1016/0092‑8674(95)90151‑5 8548812
    [Google Scholar]
  20. Fei H. Okano H.J. Li C. Lee G.H. Zhao C. Darnell R. Friedman J.M. Anatomic localization of alternatively spliced leptin receptors (Ob-R) in mouse brain and other tissues. Proc. Natl. Acad. Sci. USA 1997 94 13 7001 7005 10.1073/pnas.94.13.7001 9192681
    [Google Scholar]
  21. Moran O. Phillip M. Leptin: Obesity, diabetes and other peripheral effects - a review. Pediatr. Diabetes 2003 4 2 101 109 10.1034/j.1399‑5448.2003.00017.x 14655266
    [Google Scholar]
  22. Garofalo C. Surmacz E. Leptin and cancer. J. Cell. Physiol. 2006 207 1 12 22 10.1002/jcp.20472 16110483
    [Google Scholar]
  23. Košuta I. Mrzljak A. Kolarić B. Vučić Lovrenčić 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. 2020 9 2 560 10.3390/jcm9020560 32092909
    [Google Scholar]
  24. Martínez-Uña M. López-Mancheño Y. Diéguez C. Fernández-Rojo M.A. Novelle M.G. Unraveling the role of leptin in liver function and its relationship with liver diseases. Int. J. Mol. Sci. 2020 21 24 9368 10.3390/ijms21249368 33316927
    [Google Scholar]
  25. Floreani A. Variola A. Niro G. Premoli A. Baldo V. Gambino R. Musso G. Cassader M. Bo S. Ferrara F. Caroli D. Rizzotto E.R. Durazzo M. Plasma adiponectin levels in primary biliary cirrhosis: A novel perspective for link between hypercholesterolemia and protection against atherosclerosis. Am. J. Gastroenterol. 2008 103 8 1959 1965 10.1111/j.1572‑0241.2008.01888.x 18564121
    [Google Scholar]
  26. Goit R.K. Taylor A.W. Lo A.C.Y. The central melanocortin system as a treatment target for obesity and diabetes: A brief overview. Eur. J. Pharmacol. 2022 924 174956 10.1016/j.ejphar.2022.174956 35430211
    [Google Scholar]
  27. Shaffer E.A. Epidemiology and risk factors for gallstone disease: Has the paradigm changed in the 21st century? Curr. Gastroenterol. Rep. 2005 7 2 132 140 10.1007/s11894‑005‑0051‑8 15802102
    [Google Scholar]
  28. Ito E. Iha K. Yoshimura T. Nakaishi K. Watabe S. Early diagnosis with ultrasensitive ELISA. Adv. Clin. Chem. 2021 101 121 133 10.1016/bs.acc.2020.06.002 33706887
    [Google Scholar]
  29. Peng P. Liu C. Li Z. Xue Z. Mao P. Hu J. Xu F. Yao C. You M. Emerging ELISA derived technologies for in vitro diagnostics. Trends Analyt. Chem. 2022 152 116605 10.1016/j.trac.2022.116605
    [Google Scholar]
  30. Francisco V. Pino J. Campos-Cabaleiro V. Ruiz-Fernández C. Mera A. Gonzalez-Gay M.A. Gómez R. Gualillo O. O. GualilloObesity, fat mass and immune system: Role for leptin. Front. Physiol. 2018 9 640 10.3389/fphys.2018.00640 29910742
    [Google Scholar]
  31. Voumvouraki A. Koulentaki M. Notas G. Sfakianaki O. Kouroumalis E. Serum surrogate markers of liver fibrosis in primary biliary cirrhosis. Eur. J. Intern. Med. 2011 22 1 77 83 10.1016/j.ejim.2010.10.002 21238899
    [Google Scholar]
  32. Szalay F. Folhoffer A. Horváth A. Csak T. Speer G. Nagy Z. Lakatos P. Horváth C. Habior A. Tornai I. Lakatos P.L. Serum leptin, soluble leptin receptor, free leptin index and bone mineral density in patients with primary biliary cirrhosis. Eur. J. Gastroenterol. Hepatol. 2005 17 9 923 928 10.1097/00042737‑200509000‑00007 16093869
    [Google Scholar]
  33. Ben-Ari Z. Schafer Z. Sulkes J. Manhaim V. Tur-Kaspa R. Fainaru M. Alterations in serum leptin in chronic liver disease. Dig. Dis. Sci. 2002 47 1 183 189 10.1023/A:1013248427783 11837722
    [Google Scholar]
  34. Owecki M. Nikisch E. Miczke A. Pupek-Musialik D. Sowiński J. 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. 2010 42 8 585 589 10.1055/s‑0030‑1253422 20455195
    [Google Scholar]
  35. Séron K. Corset L. Vasseur F. Boutin P. Gómez-Ambrosi J. Salvador J. Frühbeck G. Froguel P. 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. 2006 348 4 1232 1238 10.1016/j.bbrc.2006.07.068 16920065
    [Google Scholar]
  36. Burns B. Schmidt K. Williams S.R. Kim S. Girirajan S. Elsea S.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. 2010 19 20 4026 4042 10.1093/hmg/ddq317 20663924
    [Google Scholar]
  37. Tsao D. Thomsen H.K. Chou J. Stratton J. Hagen M. Loo C. Garcia C. Sloane D.L. Rosenthal A. Lin J.C. TrkB agonists ameliorate obesity and associated metabolic conditions in mice. Endocrinology 2008 149 3 1038 1048 10.1210/en.2007‑1166 18063676
    [Google Scholar]
  38. The novel selective Pan-TRK inhibitor ONO-7579 exhibits antitumor efficacy against human gallbladder cancer in vitro Anticancer Res. 2018 38 4
    [Google Scholar]
  39. Yeo G.S.H. Connie Hung C.C. Rochford J. Keogh J. Gray J. Sivaramakrishnan S. O’Rahilly S. Farooqi I.S. A de novo mutation affecting human TrkB associated with severe obesity and developmental delay. Nat. Neurosci. 2004 7 11 1187 1189 10.1038/nn1336 15494731
    [Google Scholar]
  40. Xiong L. Deng X. Wen Y. Yang Z. Miao X. Association of BDNF and BMPR1A with clinicopathologic parameters in benign and malignant gallbladder lesions. World J. Surg. Oncol. 2013 11 1 80 10.1186/1477‑7819‑11‑80 23531103
    [Google Scholar]
  41. Kawamoto M. Onishi H. Ozono K. Yamasaki A. Imaizumi A. Nakamura M. TrkB/BDNF signaling promotes EMT mediated invasiveness and is a potential therapeutic target for gallbladder cancer. Ann. Oncol. 2016 27 vi236 10.1093/annonc/mdw371.93
    [Google Scholar]
  42. de Souza F.S.J. Santangelo A.M. Bumaschny V. Avale M.E. Smart J.L. Low M.J. Rubinstein M. Identification of neuronal enhancers of the proopiomelanocortin gene by transgenic mouse analysis and phylogenetic footprinting. Mol. Cell. Biol. 2005 25 8 3076 3086 10.1128/MCB.25.8.3076‑3086.2005 15798195
    [Google Scholar]
  43. Zhou S. Chen W. Bai X. Chen J. Xu Q. Dong L. Chen W. Qu Q. He X. Upregulation of hypothalamic POMC neurons after biliary diversion in GK rats. Front. Endocrinol. (Lausanne) 2022 13 999928 10.3389/fendo.2022.999928 36277690
    [Google Scholar]
  44. Nf-kappa B. The anti-metastatic potential of POMC gene transfer in melanoma. Mol. Ther. 2008 16 1
    [Google Scholar]
  45. Faccioli N. Poitou C. Clément K. Dubern B. Current treatments for patients with genetic obesity. J. Clin. Res. Pediatr. Endocrinol. 2023 15 2 108 119 10.4274/jcrpe.galenos.2023.2023‑3‑2 37191347
    [Google Scholar]
  46. Shabanzadeh D.M. Skaaby T. Sørensen L.T. Eugen-Olsen J. Jørgensen T. Metabolic biomarkers and gallstone disease – a population-based study. Scand. J. Gastroenterol. 2017 52 11 1270 1277 10.1080/00365521.2017.1365166 28799434
    [Google Scholar]
  47. Yeo G.S.H. Chao D.H.M. Siegert A.M. Koerperich Z.M. Ericson M.D. Simonds S.E. Larson C.M. Luquet S. Clarke I. Sharma S. Clément K. Cowley M.A. Haskell-Luevano C. Van Der Ploeg L. Adan R.A.H. The melanocortin pathway and energy homeostasis: From discovery to obesity therapy. Mol. Metab. 2021 48 101206 10.1016/j.molmet.2021.101206 33684608
    [Google Scholar]
  48. Baldini G. Phelan K.D. The melanocortin pathway and control of appetite-progress and therapeutic implications. J. Endocrinol. 2019 241 1 R1 R33 10.1530/JOE‑18‑0596 30812013
    [Google Scholar]
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Leptin/Melanocortin Pathway in Cholelithiasis Patients: A Diagnostic Perspective?
Bentham Science Publishers ; https://doi.org/10.2174/0109298665343979241025114114
/content/journals/ppl/10.2174/0109298665343979241025114114
/content/journals/ppl/10.2174/0109298665343979241025114114
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  • Article Type:     Research Article
Keywords: leptin-melanocortin pathway ; POMC ; LEP ; MC4R ; BDNF ; LEPR ; ELİSA ; TrkB ; Cholelithiasis

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