SGLT-2 Inhibitors in NAFLD: Expanding Their Role beyond Diabetes and Cardioprotection

Unit of Molecular Endocrinology, Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece

Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK

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Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK

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Laboratory of Dietetics and Quality of Life, Department of Food Science and Human Nutrition, School of Food and Nutritional Sciences, Agricultural University of Athens, 11855 Athens, Greece

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Centre for Sport, Exercise and Life Sciences, Research Institute for Health & Wellbeing, Coventry University, Coventry CV1 5FB, UK

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Aston Medical School, College of Health and Life Sciences, Aston University, Birmingham B4 7ET, UK

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2nd Department of Radiology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece

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Endocrine Oncology Unit, 1st Department of Propaedeutic Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Academic Editor: Yoshio Sumida

Int. J. Mol. Sci. 2022, 23(6), 3107; https://doi.org/10.3390/ijms23063107

Received: 9 February 2022 / Revised: 3 March 2022 / Accepted: 9 March 2022 / Published: 13 March 2022

(This article belongs to the Special Issue Atherosclerotic and Cardiometabolic Disease: From Molecular Basis to Therapeutic Advances)

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Abstract

Non-alcoholic fatty liver disease (NAFLD) is an ‘umbrella’ term, comprising a spectrum ranging from benign, liver steatosis to non-alcoholic steatohepatitis, liver fibrosis and eventually cirrhosis and hepatocellular carcinoma. NAFLD has evolved as a major health problem in recent years. Discovering ways to prevent or delay the progression of NAFLD has become a global focus. Lifestyle modifications remain the cornerstone of NAFLD treatment, even though various pharmaceutical interventions are currently under clinical trial. Among them, sodium-glucose co-transporter type-2 inhibitors (SGLT-2i) are emerging as promising agents. Processes regulated by SGLT-2i, such as endoplasmic reticulum (ER) and oxidative stress, low-grade inflammation, autophagy and apoptosis are all implicated in NAFLD pathogenesis. In this review, we summarize the current understanding of the NAFLD pathophysiology, and specifically focus on the potential impact of SGLT-2i in NAFLD development and progression, providing current evidence from in vitro, animal and human studies. Given this evidence, further mechanistic studies would advance our understanding of the exact mechanisms underlying the pathogenesis of NAFLD and the potential beneficial actions of SGLT-2i in the context of NAFLD treatment. View Full-Text

Keywords: non-alcoholic fatty liver disease; NAFLD; MAFLD; SGLT-2; sodium-glucose co-transporter type-2 inhibitors; metabolic syndrome

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MDPI and ACS Style

Androutsakos, T.; Nasiri-Ansari, N.; Bakasis, A.-D.; Kyrou, I.; Efstathopoulos, E.; Randeva, H.S.; Kassi, E. SGLT-2 Inhibitors in NAFLD: Expanding Their Role beyond Diabetes and Cardioprotection. Int. J. Mol. Sci. 2022, 23, 3107. https://doi.org/10.3390/ijms23063107

AMA Style

Androutsakos T, Nasiri-Ansari N, Bakasis A-D, Kyrou I, Efstathopoulos E, Randeva HS, Kassi E. SGLT-2 Inhibitors in NAFLD: Expanding Their Role beyond Diabetes and Cardioprotection. International Journal of Molecular Sciences. 2022; 23(6):3107. https://doi.org/10.3390/ijms23063107

Chicago/Turabian Style

Androutsakos, Theodoros, Narjes Nasiri-Ansari, Athanasios-Dimitrios Bakasis, Ioannis Kyrou, Efstathios Efstathopoulos, Harpal S. Randeva, and Eva Kassi. 2022. "SGLT-2 Inhibitors in NAFLD: Expanding Their Role beyond Diabetes and Cardioprotection" International Journal of Molecular Sciences 23, no. 6: 3107. https://doi.org/10.3390/ijms23063107

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SGLT-2 Inhibitors in NAFLD: Expanding Their Role beyond Diabetes and Cardioprotection

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