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Review
. 2023 Feb;27(2):35.
doi: 10.3892/mmr.2022.12922. Epub 2022 Dec 23.

Role of the AMPK/SIRT1 pathway in non‑alcoholic fatty liver disease (Review)

Putri Anggreini  1 , Hadi Kuncoro  2 , Sri Adi Sumiwi  3 , Jutti Levita  3
Affiliations
Review

Role of the AMPK/SIRT1 pathway in non‑alcoholic fatty liver disease (Review)

Putri Anggreini et al. Mol Med Rep. 2023 Feb.

Abstract

Non‑alcoholic fatty liver disease (NAFLD) is an increasingly prevalent ailment worldwide. Moreover, de novo lipogenesis (DNL) is considered a critical factor in the development of NAFLD; hence, its inhibition is a promising target for the prevention of fatty liver disease. There is evidence to indicate that AMP‑activated protein kinase (AMPK) and sirtuin 1 (SIRT1) may play a crucial role in DNL and are the regulatory proteins in type 2 diabetes mellitus, obesity and cardiovascular disease. Therefore, AMPK and SIRT1 may be promising targets for the treatment of NAFLD. The present review article thus aimed to summarize the findings of clinical studies published during the past decade that suggested the beneficial effects of AMPK and SIRT1, using their specific activators and their combined effects on fatty liver disease.

Keywords: AMP‑activated protein kinase; mechanism; non‑alcoholic fatty liver disease; randomized control trial; sirtuin 1.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1.
Figure 1.
Flowchart for the literature search.
Figure 2.
Figure 2.
Schematic overview of DNL and its transcriptional regulation. Carbohydrates, including glucose or fructose enter hepatocyte cells and become a sensor for DNL activation. Glucose is converted to G6P followed by isomerization to F6P and F2,6P through the glycolysis process. By contrast, fructose also converts to Gly-3P through fructolysis and further converts to F2,6P. G6P and F2,6P induce dephosphorylation of ChREBP, and it detaches from 14-3-3 protein into an active form. Moreover, the activation of insulin receptor leads to the phosphorylation of IRS1, further activating the mTORC pathway and induces the nuclear translocation of SREBP1c. In the feedback response, SIRT1 and AMPK prevent the nuclear translocation of ChREBP and SREBP1c, resulting in the inhibition of DNL transcriptional regulation. DNL, de novo lipogenesis; G6P, glucose 6-phosphate; F6P, fructose 6-phosphate; Gly-3P, glycerol 3-phosphate; F2,6P, fructose 2,6-bisphosphate; ChREBP, carbohydrate response element-binding protein; IRS1, insulin receptor substrate 1; mTORC, mammalian target of rapamycin complex; SREBP1c, sterol regulatory element-binding protein 1c; SIRT1, Sirtuin 1; AMPK, AMP-activated protein kinase.
Table II.
Table II.
Chemical structure and mechanisms of action of activators.
See this image and copyright information in PMC

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MeSH terms

Grants and funding

The present study was funded by the Doctoral Research Grant (PDD) 2022 provided by the Indonesian Ministry of Education and Culture (Grant nos. 094/E5/PG.02.00.PT/2022 and 044/E5/RA.02.00.PM/2022).
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