Secreted proteins in treating metabolic dysfunction-associated steatotic liver disease: from bench towards bedside.

Yeping HUANG; Bin LIU; Cheng HU; Yan LU

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Secreted proteins in treating metabolic dysfunction-associated steatotic liver disease: from bench towards bedside.

Author: Yeping HUANG ¹ ; Bin LIU ² ; Cheng HU ¹ ; Yan LU ³
Author Information

1. Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.
2. Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang 222005, China.
3. Institute of Metabolism and Regenerative Medicine, Digestive Endoscopic Center, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.
Publication Type:Review
Keywords: clinical application; hepatic lipid metabolism; metabolic dysfunction-associated steatohepatitis; metabolic dysfunction-associated steatotic liver disease; secreted proteins
MeSH: Humans; Fatty Liver/pathology*; Animals; Lipid Metabolism; Glucose/metabolism*
From: Protein & Cell 2025;16(8):641-666
CountryChina
Language:English
Abstract: Metabolic dysfunction-associated steatotic liver disease (MASLD) has become a global epidemic, yet effective pharmacological treatments remain limited. Secreted proteins play diverse roles in regulating glucose and lipid metabolism, and their dysregulation is implicated in the development of various metabolic diseases, including MASLD. Therefore, targeting secreted proteins and modulating associated signaling pathways represents a promising therapeutic strategy for MASLD. In this review, we summarize recent findings on the roles of emerging families of secreted proteins in MASLD and related metabolic disorders. These include the orosomucoid (ORM) family, secreted acidic cysteine rich glycoprotein (SPARC) family, neuregulin (Nrg) family, growth differentiation factor (GDF) family, interleukin (IL) family, fibroblast growth factor (FGF) family, bone morphogenic protein (BMP) family, as well as isthmin-1 (Ism1) and mesencephalic astrocyte-derived neurotrophic factor (MANF). The review highlights their impact on glucose and lipid metabolism and discusses the clinical potential of targeting these secreted proteins as a therapeutic approach for MASLD.