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Role of Renin-Angiotensin System in the Pathogenesis and Progression of Non-alcoholic Fatty Liver

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The Renin Angiotensin System in Cancer, Lung, Liver and Infectious Diseases

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 25))

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver diseases and is increasing simultaneously with obesity and Type 2 Diabetes Mellitus, which are on the rise. Currently, no FDA-approved drug exists to treat NAFLD, and pharmacological treatments are directed at managing its associated comorbidities. Therefore, a better understanding of NAFLD pathogenesis and converging pathways helps in improving prognosis and preventing progression to non-alcoholic steatohepatitis (NASH). Renin-angiotensin system (RAS) plays an important role not only in regulating blood pressure but was also found to contribute to obesity, insulin resistance, lipotoxicity, and inflammation, which are considered the key players in NAFLD pathogenesis. Moreover, a prominent role of RAS has been identified in hepatic fibrosis; activated hepatic stellate cells (HSC) express renin, angiotensin-converting enzyme (ACE), and angiotensin II (AngII), which cause HSC to proliferate and produce reactive oxygen species and inflammatory mediators. On the other hand, the inhibition of RAS improved insulin resistance and inhibited hepatic fibrogenesis. The maintenance of the balance between the two arms of RAS showed to play a meaningful role. One of the two arms is known as the classical arm; ACE-AngII-Angiotensin I receptor arm, and the other is the new one; ACE2/Ang1-7/Mas/MasII. Ang1-7 was found to increase insulin sensitivity and counteract the effects of AngII. Therefore, RAS blockers have emerged as a promising therapeutic modality for NAFLD. Accordingly, the present review will discuss the role of RAS in NAFLD and the potential therapeutic value of RAS modulators.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, College of Pharmacy, KSU, Riyadh, 11211, Kingdom of Saudi Arabia

    Amira M. Badr & Hala A. Attia

  2. Department of Pharmacology & Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt

    Amira M. Badr & Yasmen F. Mahran

  3. Emergency Hospital, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt

    Iman O. Sherif

  4. Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt

    Hala A. Attia

Authors
  1. Amira M. Badr
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  2. Iman O. Sherif
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  3. Yasmen F. Mahran
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  4. Hala A. Attia
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Corresponding author

Correspondence to Amira M. Badr .

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Editors and Affiliations

  1. Institute of Cardiovascular Sciences, St. Boniface Hospital, Winnipeg, MB, Canada

    Sukhwinder K. Bhullar

  2. Asper Clinical Research Institute, St. Boniface Hospital, Winnipeg, MB, Canada

    Paramjit S. Tappia

  3. Albrechtsen Research Centre, St. Boniface Hospital, Winnipeg, MB, Canada

    Naranjan S. Dhalla

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Badr, A.M., Sherif, I.O., Mahran, Y.F., Attia, H.A. (2023). Role of Renin-Angiotensin System in the Pathogenesis and Progression of Non-alcoholic Fatty Liver. In: Bhullar, S.K., Tappia, P.S., Dhalla, N.S. (eds) The Renin Angiotensin System in Cancer, Lung, Liver and Infectious Diseases. Advances in Biochemistry in Health and Disease, vol 25. Springer, Cham. https://doi.org/10.1007/978-3-031-23621-1_10

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