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The role of SPARC (secreted protein acidic and rich in cysteine) in the pathogenesis of obesity, type 2 diabetes, and non-alcoholic fatty liver disease

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Abstract

Secreted protein acidic and rich in cysteine (SPARC) is an extracellular matrix glycoprotein with pleiotropic functions, which is expressed in adipose, hepatic, muscular, and pancreatic tissue. Particularly, several studies demonstrated that SPARC is an important player in the context of obesity, diabetes, and fatty liver disease including advanced hepatic fibrosis and hepatocellular carcinoma. Evidence in murine and human samples indicates that SPARC is involved in adipogenesis, cellular metabolism, extracellular matrix modulation, glucose and lipid metabolism, among others. Furthermore, studies in SPARC knockout mouse model showed that SPARC contributes to adipose tissue formation, non-alcoholic fatty liver disease (NAFLD), and diabetes. Hence, SPARC may represent a novel and interesting target protein for future therapeutic interventions or a biomarker of disease progression. This review summarizes the role of SPARC in the pathophysiology of obesity, and extensively revised SPARC functions in physiological and pathological adipose tissue deposition, muscle metabolism, liver, and diabetes-related pathways.

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Funding

This work was supported by Austral University and Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT) grants PICT 2018/03097 (CA) and PICT 2018/ 4053 (GM).

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  1. Gene Therapy Laboratory, Facultad de Ciencias Biomédicas, Instituto de Investigaciones en Medicina Traslacional, CONICET- Universidad Austral, Av. Pte. Perón 1500 (B1629AHJ) Derqui-Pilar, Buenos Aires, Argentina

    Catalina Atorrasagasti, Agostina M. Onorato & Guillermo Mazzolini

  2. Liver Unit, Hospital Universitario Austral, Universidad Austral, Av. Pte. Perón 1500 (B1629AHJ) Derqui-Pilar, Buenos Aires, Argentina

    Guillermo Mazzolini

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Catalina Atorrasagasti and Guillermo Mazzolini shared credits for senior authorship.

Key points

- SPARC is an important protein involved in different biological processes including obesity-associated disorders.

- SPARC may act both in ECM modulation and in the regulation of cell environment interactions inhibiting adipogenesis.

- SPARC contributes to adipose tissue formation, non-alcoholic fatty liver disease (NAFLD), and diabetes.

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Atorrasagasti, C., Onorato, A.M. & Mazzolini, G. The role of SPARC (secreted protein acidic and rich in cysteine) in the pathogenesis of obesity, type 2 diabetes, and non-alcoholic fatty liver disease. J Physiol Biochem 79, 815–831 (2023). https://doi.org/10.1007/s13105-022-00913-5

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