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

Öz

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.

Anahtar Kelimeler

• Progranülin
• Adipokin
• İnflamasyon
• Obezite
• Metabolik sendrom
• İnsülin direnci

Destekleyen Kurum

Bu araştırma herhangi bir kamu, ticari veya kar amacı gütmeyen kuruluştan özel bir hibe almamıştır.

Etik Beyan

Bu çalışma, daha önce yayımlanmış literatüre dayanan bir derleme makalesidir. İnsan veya hayvan deneği içermediğinden etik kurul onayı gerekmemektedir.

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

Öz

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.

Anahtar Kelimeler

• Progranulin
• Adipokine
• Inflammation
• Obesity
• Metabolic syndrome
• Insulin resistance

Destekleyen Kurum

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Etik Beyan

This study is a narrative review article based on previously published literature. No ethical approval was required as no human or animal subjects were involved.

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