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Dergiler / Atlas Journal of Medicine / 2026 / Cilt: 6 Sayı: 3

Progranülin: İnflamasyon, obezite ve metabolik sendromun kesişiminde yeni bir biyobelirteç

Progranulin: A novel biomarker at the intersection of inflammation, obesity, and metabolic syndrome

Sena Öner(İSTANBUL ÜNİVERSİTESİ - CERRAHPAŞA, CERRAHPAŞA TIP FAKÜLTESİ)0000-0002-1726-6679
Özlem Balci(İSTANBUL ÜNİVERSİTESİ-CERRAHPAŞA, CERRAHPAŞA TIP FAKÜLTESİ, CERRAHPAŞA TIP PR.)0000-0001-7432-9915
Sayfa
198–205
Yayın Tarihi
2026-10-28
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Yapay Zeka Hızlı Bakış & Çıkarımlar

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⚡ TL;DR(1 Cümlede Hızlı Çıkarım)

Dolaşımdaki PGRN düzeyleri obezitede yükselmiş olup vücut kütle indeksi, insülin direnci, trigliseritler ve C-reaktif protein ile pozitif korelasyon göstermektedir.

📌 3 Maddede Bu Makale

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Amaç & Hipotez:Progranülin (PGRN), GRN geni tarafından kodlanan 593 amino asitlik, sisteince zengin bir sekretuar glikoproteindir.
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Temel Bulgular & Veri:Protein, tümör nekroz faktör reseptörlerine (TNFR1 ve TNFR2) bağlanarak TNF-α aracılığı ile NF-κB ve PI3K/Akt yolakları üzerinden gerçekleşen inflamatuvar sinyal iletimini bloke eder.
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Sonuç & Katkı:Dolaşımdaki PGRN düzeyleri obezitede yükselmiş olup vücut kütle indeksi, insülin direnci, trigliseritler ve C-reaktif protein ile pozitif korelasyon göstermektedir.
🔬Tür:Literatür & Derleme Çalışması
📍Kapsam:Genişletilmiş Akademik Örneklem
⚙️Değişkenler:Progranülin · Adipokin · İnflamasyon

Özet

Progranülin (PGRN), GRN geni tarafından kodlanan 593 amino asitlik, sisteince zengin bir sekretuar glikoproteindir. Başlangıçta nörodejeneratif hastalıklarla ilişkili olarak incelenen PGRN, son on yılda geniş metabolik öneme sahip çok fonksiyonlu bir adipokin olarak kabul görmüştür. Protein, tümör nekroz faktör reseptörlerine (TNFR1 ve TNFR2) bağlanarak TNF-α aracılığı ile NF-κB ve PI3K/Akt yolakları üzerinden gerçekleşen inflamatuvar sinyal iletimini bloke eder. Tam uzunluktaki PGRN anti-inflamatuvar özellik gösterirken, proteolitik parçalanma ürünleri olan granülin peptitleri pro-inflamatuvar etki gösterir. Bu fonksiyonel ikili yapı, hem ölçümü hem de yorumlamayı zorlaştırmaktadır. Dolaşımdaki PGRN düzeyleri obezitede yükselmiş olup vücut kütle indeksi, insülin direnci, trigliseritler ve C-reaktif protein ile pozitif korelasyon göstermektedir. Mekanistik çalışmalar, PGRN'ın IL-6/STAT3 bağımlı IRS-1 fosforilasyonunu bozarak insülin direncini tetiklediğini ortaya koymuştur. Klinik çalışmalar PGRN'ın tip 2 diyabet, polikistik over sendromu, alkole bağlı olmayan yağlı karaciğer hastalığı ve kardiyovasküler patoloji ile ilişkisini göstermiştir. Diyet müdahaleleri ve bariatrik cerrahi PGRN düzeylerini düşürebilmektedir. Atsttrin, mühendislik ürünü bir PGRN türevi olarak preklinik çalışmalarda umut verici sonuçlar göstermektedir. Bu derleme, PGRN biyolojisi, inflamatuvar sinyal mekanizmaları, metabolik rolleri, beslenme modülasyonu ve terapotik potansiyelini, mevcut kanıtları sınırlayan metodolojik kısıtlamalara dikkat çekerek sentezlemektedir.

Abstract

Progranulin (PGRN) is a 593-amino acid, cysteine-rich glycoprotein encoded by the GRN gene on chromosome 17q21. Long studied in neurodegenerative disease, PGRN has gained recognition as an adipokine with broad metabolic relevance. The protein binds tumor necrosis factor receptors (TNFR1 and TNFR2), blocking TNF-α–mediated signaling through NF-κB and PI3K/Akt cascades. Full-length PGRN is anti-inflammatory; its proteolytic cleavage products—granulin peptides—are not. This functional duality complicates both measurement and interpretation. Circulating PGRN is elevated in obesity, correlating with body mass index, insulin resistance, triglycerides, and C-reactive protein. Mechanistic work indicates that PGRN promotes insulin resistance via IL-6/STAT3-dependent disruption of insulin receptor substrate-1 phosphorylation. Clinical associations extend to type 2 diabetes, polycystic ovary syndrome, non-alcoholic fatty liver disease, and cardiovascular pathology. Dietary interventions and bariatric surgery can lower PGRN levels, though whether these reductions translate into improved outcomes remains unproven. Atsttrin, an engineered PGRN derivative, shows preclinical promise. This review synthesizes evidence on PGRN biology, inflammatory signaling, metabolic roles, nutritional modulation, and therapeutic prospects, with attention to the methodological limitations that constrain current conclusions.

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Bu Makaleye Atıf Yap

Öner, S., Balci, Ö. (2026). Progranülin: İnflamasyon, obezite ve metabolik sendromun kesişiminde yeni bir biyobelirteç. Atlas Journal of Medicine, Cilt: 6 Sayı: 3, 198–205. https://doi.org/10.54270/atljm.2026.139

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Kaynakça (40)

  1. World Health Organization. Obesity and overweight fact sheet. Published March 2024. Accessed January 2026. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
  2. Hotamisligil GS. Inflammation, metaflammation and immunometabolic disorders. Nature. 2017;542(7640):177-85.
  3. Alberti KGMM, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome: a joint interim statement. Circulation. 2009;120(16):1640-5.
  4. Rosen ED, Spiegelman BM. What we talk about when we talk about fat. Cell. 2014;156(1-2):20-44.
  5. Fasshauer M, Blüher M. Adipokines in health and disease. Trends Pharmacol Sci. 2015;36(7):461-70.
  6. Ouchi N, Parker JL, Lugus JJ, et al. Adipokines in inflammation and metabolic disease. Nat Rev Immunol. 2011;11(2):85-97.
  7. Bateman A, Bennett HP. The granulin gene family: from cancer to dementia. BioEssays. 2009;31(11):1245-54.
  8. He Z, Bateman A. Progranulin (granulin-epithelin precursor, PC-cell-derived growth factor, acrogranin) mediates tissue repair and tumorigenesis. J Mol Med. 2003;81(10):600-12.
  9. Daniel R, He Z, Carmichael KP, et al. Cellular localization of gene expression for progranulin. J Histochem Cytochem. 2000;48(7):999-1009.
  10. Baker M, Mackenzie IR, Pickering-Brown SM, et al. Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature. 2006;442(7105):916-9.
  11. Tang W, Lu Y, Tian QY, et al. The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice. Science. 2011;332(6028):478-84.
  12. Matsubara T, Mita A, Minami K, et al. PGRN is a key adipokine mediating high fat diet-induced insulin resistance and obesity through IL-6 in adipose tissue. Cell Metab. 2012;15(1):38-50.
  13. Zhu J, Nathan C, Jin W, et al. Conversion of proepithelin to epithelins: roles of SLPI and elastase in host defense and wound repair. Cell. 2002;111(6):867-78.
  14. Korolczuk A, Bełtowski J. Progranulin, a new adipokine at the crossroads of metabolic syndrome, diabetes, dyslipidemia and hypertension. Curr Pharm Des. 2017;23(10):1533-9.
  15. Nguyen AD, Nguyen TA, Martens LH, et al. Progranulin: at the interface of neurodegenerative and metabolic diseases. Trends Endocrinol Metab. 2013;24(12):597-606.
  16. Huang G, Jian J, Liu CJ. Progranulinopathy: a diverse realm of disorders linked to progranulin imbalances. Cytokine Growth Factor Rev. 2024;76:142-59.
  17. Cenik B, Sephton CF, Kutluk Cenik B, et al. Progranulin: a proteolytically processed protein at the crossroads of inflammation and neurodegeneration. J Biol Chem. 2012;287(39):32298-306.
  18. Jian J, Li G, Hettinghouse A, et al. Progranulin: a key player in autoimmune diseases. Cytokine. 2018;101:48-55.
  19. Youn BS, Bang SI, Klöting N, et al. Serum progranulin concentrations may be associated with macrophage infiltration into omental adipose tissue. Diabetes. 2009;58(3):627-36.
  20. Qu H, Deng H, Hu Z. Plasma progranulin concentrations are increased in patients with type 2 diabetes and obesity and correlated with insulin resistance. Mediators Inflamm. 2013;2013:360190.
  21. Lee CW, Stankowski JN, Chew J, et al. The lysosomal protein cathepsin L is a progranulin protease. Mol Neurodegener. 2017;12(1):55.
  22. Paushter DH, Du H, Feng T, et al. The lysosomal function of progranulin, a guardian against neurodegeneration. Acta Neuropathol. 2018;136(1):1-17.
  23. Wang BC, Liu H, Talwar A, et al. New discovery rarely runs smooth: an update on progranulin/TNFR interactions. Protein Cell. 2015;6(11):792-803.
  24. Wang X, Liang Y, Yang F, et al. Molecular mechanisms and targeted therapy of progranulin in metabolic diseases. Front Endocrinol. 2025;16:1553794.
  25. Chen X, Chang J, Deng Q, et al. Progranulin does not bind tumor necrosis factor (TNF) receptors and is not a direct regulator of TNF-dependent signaling. J Neurosci. 2013;33(21):9202-13.
  26. Jian J, Konopka J, Liu C. Insights into the role of progranulin in immunity, infection, and inflammation. J Leukoc Biol. 2013;93(2):199-208.
  27. Liu L, Guo H, Song A, et al. Progranulin inhibits LPS-induced macrophage M1 polarization via NF-κB and MAPK pathways. BMC Immunol. 2020;21(1):32.
  28. Lee CH, Park CB, Kim HK, et al. Macrophage-specific progranulin deficiency prevents diet-induced obesity. Diabetes Metab J. 2025;49(4):784-97.
  29. Yin F, Banerjee R, Thomas B, et al. Exaggerated inflammation, impaired host defense, and neuropathology in progranulin-deficient mice. J Exp Med. 2010;207(1):117-28.
  30. Murakoshi M, Gohda T, Adachi E, et al. Differential organ-specific inflammatory response to progranulin in high-fat diet-fed mice. Sci Rep. 2021;11(1):1194.
  31. Zhou B, Li H, Liu J, et al. Progranulin induces adipose insulin resistance and autophagic imbalance via TNFR1 in mice. J Mol Endocrinol. 2015;55(3):231-43.
  32. Richter J, Focke D, Ebert T, et al. Serum levels of the adipokine progranulin depend on renal function. Diabetes Care. 2013;36(2):410-4.
  33. Todoric J, Handisurya A, Perkmann T, et al. Circulating progranulin levels in women with gestational diabetes mellitus. Eur J Endocrinol. 2012;167(4):561-7.
  34. Uzdogan A, Kuru Pekcan M, Cil AP, et al. Progranulin and tumor necrosis factor-alpha in lean polycystic ovary syndrome patients. Gynecol Endocrinol. 2021;37(10):925-9.
  35. Qiao G, Lu Y, Wu J, et al. Progranulin’s protective mechanisms and therapeutic potential in cardiovascular disease. Cells. 2025;14(11):762.
  36. Kojima Y, Ono K, Inoue K, et al. Progranulin expression in advanced human atherosclerotic plaque. Atherosclerosis. 2009;206(1):102-8.
  37. Yilmaz Y, Eren F, Yonal O, et al. Serum progranulin as an independent marker of liver fibrosis in biopsy-proven nonalcoholic fatty liver disease. Dis Markers. 2011;31(4):205-10.
  38. Yoo W, Lee J, Noh KH, et al. Progranulin attenuates liver fibrosis by downregulating the inflammatory response. Cell Death Dis. 2019;10(10):758.
  39. Nicoletto BB, Sarmento RA, Pedrollo EF, et al. Association between progranulin serum levels and dietary intake. PLoS One. 2018;13(8):e0202149.
  40. Kraemer MdS, Moehlecke M, Rheinheimer J, et al. Plasma progranulin levels in obese patients before and after Roux-en-Y gastric bariatric surgery. Surg Obes Relat Dis. 2020;16(11):1655-6.