Penargetan Terapeutik Aksis AMPK–SREBP pada Disregulasi Metabolisme Lemak: Implikasinya terhadap Sindrom Metabolik dan NAFLD

Sri Octa Handayani; Shellya Puti Sudesty

doi:10.59923/healthcare.v1i1.739

Authors

Sri Octa Handayani Program Studi Kedokteran, Universitas Lampung, Indonesia
Shellya Puti Sudesty Program Studi Kedokteran, Universitas Lampung, Indonesia

DOI:

https://doi.org/10.59923/healthcare.v1i1.739

Keywords:

AMPK, SREBP-1c, Sindrom metabolik, NAFLD, Metabolisme Lipid

Abstract

Disregulasi metabolisme lemak merupakan mekanisme utama dalam patogenesis sindrom metabolik dan non-alcoholic fatty liver disease (NAFLD), yang prevalensinya terus meningkat secara global. Aksis AMP-activated protein kinase (AMPK)–sterol regulatory element-binding protein (SREBP) berperan penting dalam menjaga keseimbangan antara lipogenesis dan oksidasi asam lemak. Review ini bertujuan untuk mengkaji peran molekuler aksis AMPK–SREBP dalam disregulasi metabolisme lipid serta mengevaluasi potensi intervensi terapeutik yang menargetkan jalur tersebut pada sindrom metabolik dan NAFLD. Penelitian disusun sebagai structured narrative review dengan penelusuran literatur melalui PubMed, Scopus, dan Web of Science pada periode 2020–2025. Hasil kajian menunjukkan bahwa peningkatan aktivitas SREBP-1c dan penurunan aktivasi AMPK berkontribusi terhadap peningkatan lipogenesis, penurunan oksidasi asam lemak, serta akumulasi lipid intrahepatik. Berbagai intervensi farmakologis dan senyawa alami, termasuk kombinasi metformin–berberine, flavonoid, stilben, lignan, alkaloid, dan molekul sintetik, terbukti mengaktivasi AMPK dan menekan ekspresi SREBP-1c, sehingga memperbaiki steatosis, resistensi insulin, inflamasi, dan stres oksidatif pada model praklinis NAFLD. Secara keseluruhan, aksis AMPK–SREBP merupakan target terapeutik yang menjanjikan dalam pengendalian sindrom metabolik dan NAFLD. Meskipun sebagian besar bukti masih bersifat praklinis, konsistensi mekanisme molekuler yang dilaporkan mendukung pengembangan penelitian translasi dan uji klinis lebih lanjut.

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