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. 2025 Feb 7;44(6):1608–1640. doi: 10.1038/s44318-025-00366-8

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© The Author(s) 2025

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/. Creative Commons Public Domain Dedication waiver http://creativecommons.org/publicdomain/zero/1.0/ applies to the data associated with this article, unless otherwise stated in a credit line to the data, but does not extend to the graphical or creative elements of illustrations, charts, or figures. This waiver removes legal barriers to the re-use and mining of research data. According to standard scholarly practice, it is recommended to provide appropriate citation and attribution whenever technically possible.

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(A–D) ACC1 and PC immunofluorescence microscopy of Kif12^mut/mut mouse liver cryosections (A) and HepG2 cells transduced with scrambled control (SC) and KIF12-knockdown (KD) vectors (B), with respective statistics (C and D). Scale bars, 100 μm in A and 20 µm in (B). Error bars, mean ± SEM. Welch’s t test. Biological replicates, 12 optical fields from 3 mice (C); and individual cells (D). (E, F) ACC1 immunoblotting of HepG2 cell lysates transduced with SC and KIF12-KD vectors (E) with statistics (F). Error bars, mean ± SEM. Welch’s t test. Biological replicates, individual dishes. (G) Comparison of CPT1 activity of wild type (WT) and Kif12^mut/mut mouse livers, as an indicator of mitochondrial beta oxidation of fatty acids. Error bars, mean ± SEM. Unpaired single-sided Welch’s t test. Biological replicates, mouse individuals. (H) The working hypothesis. KIF12 deficiency may affect beta oxidation of the liver probably through the elevation of the ACC1 product, Malonyl-CoA, as well as upregulating lipid production, to promote steatosis. Corresponding to Fig. EV5.