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. 2024 Dec 9;30(12):3614–3623. doi: 10.1038/s41591-024-03284-0

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© The Author(s) 2024

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Extended Data Fig. 4 — a) In the steatotic liver-specific disease, the primary increase in the liver triglyceride content is due to the hepatic retention of very low-density lipoproteins (VLDL). This retention is causally related to liver inflammation, fibrosis, and hepatocellular carcinoma. In this type of MASLD, the higher risk of diabetes is due to the degree of liver fibrosis, while the lower risk of cardiovascular disease (CVD) to lipoprotein retention. b) In the systemic MASLD, the liver is entwined in the crosstalk among metabolic organs. In this type of MASLD, a dysfunctional visceral adipose tissue may increase the diabetes risk and may release free fatty acids that are incorporated into triglycerides in the hepatocytes causing liver steatosis. In turn, liver steatosis causes an overproduction of VLDL with a subsequent increase in circulating low-density lipoproteins (LDL) resulting in a higher risk of CVD. Additionally, the systemic MASLD associates with an increased blood pressure resulting in kidney failure and further increasing the CVD risk. This figure was created with BioRender.com. CKD: chronic kidney disease (failure); VAT: visceral adipose tissue; LD: lipid droplets.