{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:33:46Z","timestamp":1760060026396,"version":"build-2065373602"},"reference-count":46,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University of Gdansk","award":["01-30024\/0006086\/01\/304\/304\/0\/2024","61-00206\/K21\/MPK 664"],"award-info":[{"award-number":["01-30024\/0006086\/01\/304\/304\/0\/2024","61-00206\/K21\/MPK 664"]}]},{"name":"ST-534","award":["01-30024\/0006086\/01\/304\/304\/0\/2024","61-00206\/K21\/MPK 664"],"award-info":[{"award-number":["01-30024\/0006086\/01\/304\/304\/0\/2024","61-00206\/K21\/MPK 664"]}]},{"name":"ST-40","award":["01-30024\/0006086\/01\/304\/304\/0\/2024","61-00206\/K21\/MPK 664"],"award-info":[{"award-number":["01-30024\/0006086\/01\/304\/304\/0\/2024","61-00206\/K21\/MPK 664"]}]},{"name":"IDUB","award":["01-30024\/0006086\/01\/304\/304\/0\/2024","61-00206\/K21\/MPK 664"],"award-info":[{"award-number":["01-30024\/0006086\/01\/304\/304\/0\/2024","61-00206\/K21\/MPK 664"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Huntington\u2019s disease (HD) is characterized by progressive neurodegeneration, but increasing evidence points to multisystemic involvement, including early hepatic steatosis in pediatric HD. Therefore, it is important to consider systemic alterations, particularly in liver lipid metabolism. In this study, we analyzed fatty acid (FA) profiles in two symptomatic HD mouse models: 2-month-old R6\/2 mice representing early-onset HD and 22-month-old HdhQ150\/Q150 (Hdh) mice representing late-onset HD, along with age-matched wild-type (WT) controls. FA composition in liver tissue was assessed by gas chromatography\u2013mass spectrometry (GC\u2013MS). In R6\/2 mice, we observed increased levels of total iso-branched chain, monounsaturated, and n-6 polyunsaturated FAs compared to WT. In contrast, only a few FA species showed reduced concentrations in Hdh mice. Overall, our results indicate that R6\/2 mice exhibit more pronounced alterations in hepatic FA profiles than Hdh mice, suggesting that early-onset HD may be associated with more severe peripheral metabolic dysregulation.<\/jats:p>","DOI":"10.3390\/ijms26157304","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T16:00:37Z","timestamp":1753718437000},"page":"7304","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fatty Acid Profile in the Liver of Mice with Early- and Late-Onset Forms of Huntington\u2019s Disease"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6466-4859","authenticated-orcid":false,"given":"Magdalena","family":"Gregorczyk","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Clinical Physiology, Medical University of Gdansk, 80-210 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2877-5652","authenticated-orcid":false,"given":"Adriana","family":"Mika","sequence":"additional","affiliation":[{"name":"Department of Environmental Analysis, Faculty of Chemistry, University of Gdansk, 80-309 Gdansk, Poland"},{"name":"Department of Pharmaceutical Biochemistry, Medical University of Gdansk, 80-210 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9028-3790","authenticated-orcid":false,"given":"Tomasz","family":"\u015aledzi\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biochemistry, Medical University of Gdansk, 80-210 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8934-9748","authenticated-orcid":false,"given":"Marta","family":"Tomczyk","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical University of Gdansk, 80-210 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iwona","family":"Rybakowska","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Clinical Physiology, Medical University of Gdansk, 80-210 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/S0140-6736(07)60111-1","article-title":"Huntington\u2019s disease","volume":"369","author":"Walker","year":"2007","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Chang, K.-H., Cheng, M.-L., Lo, C.-J., Fan, C.-M., Wu, Y.-R., and Chen, C.-M. (2023). Alterations of Lipoprotein Profiles in the Plasma as Biomarkers of Huntington\u2019s Disease. Cells, 12.","DOI":"10.3390\/cells12030385"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Kim, A., Lalonde, K., Truesdell, A., Welter, P.C., Brocardo, P.S., Rosenstock, T.R., and Gil-Mohapel, J. (2021). New Avenues for the Treatment of Huntington\u2019s Disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168363"},{"key":"ref_4","first-page":"1202","article-title":"The Likelihood of Being Affected with Huntington Disease by a Particular Age, for Specific CAG Size","volume":"60","author":"Brinkman","year":"1997","journal-title":"Am. J. Hum. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/S1474-4422(18)30294-1","article-title":"Biological and clinical manifestations of juvenile Huntington\u2019s disease a retrospective analysis","volume":"17","author":"Fusilli","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.parkreldis.2022.08.027","article-title":"Early liver steatosis in children with pediatric Huntington disease and highly expanded CAG mutations","volume":"103","author":"Squitieri","year":"2022","journal-title":"Park. Relat. Disord."},{"key":"ref_7","first-page":"16","article-title":"Phenotypic Characterization of Individuals with 30-40 CAG Repeats in the Huntington Disease (HD) Gene Reveals HD Cases with 36 Repeats and Apparently Normal Elderly Individuals with 36-39 Repeats","volume":"59","author":"Rubinsztein","year":"1996","journal-title":"Am. J. Hum. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2551","DOI":"10.1093\/hmg\/ddaa139","article-title":"Patterns of CAG repeat instability in the central nervous system and periphery in Huntington\u2019s disease and in spinocerebellar ataxia type 1","volume":"29","author":"Pinto","year":"2020","journal-title":"Hum. Mol. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1111\/j.1471-4159.2005.03620.x","article-title":"Interaction of huntingtin fragments with brain membranes\u2014Clues to early dysfunction in Huntington\u2019s disease","volume":"96","author":"Suopanki","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Monaco, G., Van Dam, S., Ribeiro, J.L.C.N., Larbi, A., and De Magalh\u00e3es, J.P. (2015). A comparison of human and mouse gene co-expression networks reveals conservation and divergence at the tissue, pathway and disease levels. BMC Evol. Biol., 15.","DOI":"10.1186\/s12862-015-0534-7"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1038\/nrg1045","article-title":"Modelling brain diseases in mice: The challenges of design and analysis","volume":"4","author":"Watase","year":"2003","journal-title":"Nat. Rev. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.jns.2016.02.018","article-title":"Liver function in Huntington\u2019s disease assessed by blood biochemical analyses in a clinical setting","volume":"362","author":"Nielsen","year":"2016","journal-title":"J. Neurol. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1212\/WNL.0b013e318282514e","article-title":"Hepatic mitochondrial dysfunction in manifest and premanifest Huntington disease","volume":"80","author":"Goetze","year":"2013","journal-title":"Neurology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1007\/s12640-017-9766-1","article-title":"Huntington\u2019s Disease and Mitochondria","volume":"32","author":"Farshbaf","year":"2017","journal-title":"Neurotox. Res."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Carvalho, C.C.C.R., and Caramujo, M.J. (2018). The Various Roles of Fatty Acids. Molecules, 23.","DOI":"10.3390\/molecules23102583"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ravaut, G., Legiot, A., Bergeron, K.-F., and Mounier, C. (2021). Monounsaturated Fatty Acids in Obesity-Related Inflammation. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010330"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.plipres.2005.11.002","article-title":"Ceramides in insulin resistance and lipotoxicity","volume":"45","author":"Summers","year":"2006","journal-title":"Prog. Lipid Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.physbeh.2007.11.049","article-title":"Lipid accumulation in non-adipose tissue and lipotoxicity","volume":"94","author":"Herpen","year":"2008","journal-title":"Physiol. Behav."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1172\/JCI92035","article-title":"Inflammatory mechanisms linking obesity and metabolic disease","volume":"127","author":"Saltiel","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Nilsen, D.W.T., Myhre, P.L., Kalstad, A., Schmidt, E.B., Arnesen, H., and Seljeflot, I. (2021). Serum Levels of Dihomo-Gamma (\u03b3)-Linolenic Acid (DGLA) Are Inversely Associated with Linoleic Acid and Total Death in Elderly Patients with a Recent Myocardial Infarction. Nutrients, 13.","DOI":"10.3390\/nu13103475"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.plefa.2018.03.004","article-title":"Omega-6 fatty acids and inflammation","volume":"132","author":"Jacqueline","year":"2018","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_22","first-page":"577348","article-title":"Inflammation in Huntington\u2019s disease: A few new twists on an old tale","volume":"15","author":"Santos","year":"2020","journal-title":"J. Neuroimmunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1016\/j.jcmgh.2022.01.007","article-title":"Liver Steatosis is a Driving Factor of Inflammation","volume":"13","author":"Mooli","year":"2022","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Mielcarek, M., Toczek, M., Smeets, C.J.L.M., Franklin, S.A., Bondulich, M.K., Jolinon, N., Muller, T., Ahmed, M., Dick, J.R.T., and Piotrowska, I. (2015). HDAC4-myogenin axis as an important marker of HD-related skeletal muscle atrophy. PLoS Genet., 11.","DOI":"10.1371\/journal.pgen.1005021"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1016\/j.bbadis.2016.08.019","article-title":"An impaired metabolism of nucleotides underpins a novel mechanism of cardiac remodeling leading to Huntington\u2019s disease related cardiomyopathy","volume":"1862","author":"Toczek","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Tomczyk, M., Glaser, T., Slominska, E.M., Ulrich, H., and Smolenski, R.T. (2021). Purine Nucleotides Metabolism and Signaling in Huntington\u2019s Disease: Search for a Target for Novel Therapies. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126545"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1080\/15257770.2020.1815769","article-title":"Huntingtin protein maintains balanced energetics in mouse cardiomyocytes","volume":"41","author":"Tomczyk","year":"2022","journal-title":"Nucleosides Nucleotides Nucleic Acids"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"116653","DOI":"10.1016\/j.lfs.2019.116653","article-title":"Inflammatory changes in peripheral organs in the BACHD murine model of Huntington\u2019s disease","volume":"232","author":"Vieira","year":"2019","journal-title":"Life Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1093\/hmg\/ddt036","article-title":"A critical role of astrocyte-mediated nuclear factor-\u03baB-dependent inflammation in Huntington\u2019s disease","volume":"22","author":"Hsiao","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.plefa.2007.05.003","article-title":"Fatty acid composition of plasma, blood cells and whole blood: Relevance for the assessment of the fatty acid status in humans","volume":"76","author":"Eligini","year":"2007","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.jacl.2009.11.003","article-title":"Altered cholesterol and fatty acid metabolism in Huntington disease","volume":"4","author":"Block","year":"2010","journal-title":"J. Clin. Lipidol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Wei, Y., Liu, M., Li, X., Liu, J., and Li, H. (2018). Origin of the Autophagosome Membrane in Mammals Biomed. Res. Int., 1012789.","DOI":"10.1155\/2018\/1012789"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Iuliano, M., Seeley, C., Sapp, E., Jones, E.L., Martin, C., Li, X., DiFiglia, M., and Kegel-Gleason, K.B. (2021). Disposition of Proteins and Lipids in Synaptic Membrane Compartments Is Altered in Q175\/Q7 Huntington\u2019s Disease Mouse Striatum. Front. Synaptic. Neurosci., 13.","DOI":"10.3389\/fnsyn.2021.618391"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.it.2015.04.007","article-title":"The choreography of neuroinflammation in Huntington\u2019s disease","volume":"36","author":"Crotti","year":"2015","journal-title":"Trends Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Rocha, N.P., Ribeiro, F.M., Furr-Stimming, E., and Teixeira, A.L. (2016). Neuroimmunology of Huntington\u2019s Disease: Revisiting Evidence from Human Studies. Mediat. Inflamm., 8653132.","DOI":"10.1155\/2016\/8653132"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1084\/jem.20080178","article-title":"A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington\u2019s disease","volume":"205","author":"Wild","year":"2008","journal-title":"J. Exp. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1002\/glia.24188","article-title":"Orai2 channel regulates prostaglandin E2 production in TNF\u03b1\/IL1\u03b1-stimulated astrocytes","volume":"70","author":"Nakajima","year":"2022","journal-title":"Glia"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3179","DOI":"10.1158\/0008-5472.CAN-15-2658","article-title":"Membrane IL1\u03b1 Inhibits the Development of Hepatocellular Carcinoma via Promoting T- and NK-cell Activation","volume":"76","author":"Lin","year":"2016","journal-title":"Cancer Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2840","DOI":"10.4049\/jimmunol.1801653","article-title":"Anti-Inflammatory and Proresolving Effects of the Omega-6 Polyunsaturated Fatty Acid Adrenic Acid","volume":"205","author":"Brouwers","year":"2020","journal-title":"J. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"101165","DOI":"10.1016\/j.plipres.2022.101165","article-title":"Polyunsaturated fatty acids and fatty acid-derived lipid mediators: Recent advances in the understanding of their biosynthesis, structures, and functions","volume":"86","author":"Dyall","year":"2022","journal-title":"Prog. Lipid Res."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Gozdzik, P., Czumaj, A., Sledzinski, T., and Mika, A. (2023). Branched-chain fatty acids affect the expression of fatty acid synthase and C-reactive protein genes in the hepatocyte cell line. Biosci. Rep., 43.","DOI":"10.1042\/BSR20230114"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/j.bbadis.2011.05.006","article-title":"The dysfunction of hepatic transcriptional factors in mice with Huntington\u2019s Disease","volume":"1812","author":"Chiang","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.brainresbull.2006.11.004","article-title":"The Hdh Q150\/Q150 knock-in mouse model of HD and the R6\/a exon 1 model develop comparable and widespread molecular phenotypes","volume":"72","author":"Woodman","year":"2007","journal-title":"Brain Res. Bull."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1093\/hmg\/10.2.137","article-title":"Neurological abnormalities in a knock-in mouse model of Huntington\u2019s disease","volume":"10","author":"Lin","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0021-9258(18)64849-5","article-title":"A simple method for the isolation and purification of total lipides from animal tissues","volume":"226","author":"Folch","year":"1957","journal-title":"J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1002\/oby.23711","article-title":"Hepatic and serum branched-chain fatty acid profile in patients with nonalcoholic fatty liver disease: A case-control study","volume":"31","author":"Sledzinski","year":"2023","journal-title":"Obesity"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/15\/7304\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:17:36Z","timestamp":1760033856000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/15\/7304"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,28]]},"references-count":46,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["ijms26157304"],"URL":"https:\/\/doi.org\/10.3390\/ijms26157304","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2025,7,28]]}}}