{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:59:22Z","timestamp":1768510762308,"version":"3.49.0"},"reference-count":58,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science and Technology Research and Development Projects of China National Fisheries Corp.","award":["CNFCCA2025002"],"award-info":[{"award-number":["CNFCCA2025002"]}]},{"name":"APC","award":["CNFCCA2025002"],"award-info":[{"award-number":["CNFCCA2025002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background\/Objectives: Replacing fish oil with vegetable oil is an important measure for aquaculture to relieve the pressure of fish oil, but it is also easy to cause the growth decline and metabolic disorder of farmed animals, mainly due to the change in dietary fatty acids. This study investigated the regulatory effects of dietary fatty acid composition on glucose metabolism in large yellow croaker (Larimichthys crocea) with an initial weight of 30.51 \u00b1 0.16 g. Methods: Three isonitrogenous (~43% crude protein) and isolipid (~11% crude lipid) diets were formulated as follows: control (CON, DHA\/EPA-rich oil as primary lipid), moderate palmitic acid (MPA, 50% of DHA+EPA-rich oil was replaced by glyceryl palmitate), and high palmitic acid (HPA, 100% of DHA+EPA-rich oil was replaced by glyceryl palmitate). Results: After 10 weeks of feeding, the HPA significantly reduced the liver\/muscle glycogen contents, increased the liver lipid content, decreased the serum leptin\/insulin level, and increased the adiponectin level. The levels of DHA and EPA in liver were decreased significantly. Transcriptionally, HPA upregulated hepatic glucokinase (gk, glycolysis) but down-regulated glycogen synthase (gys) and insulin\/irs2 (insulin pathway) while inhibiting muscle ampk and leptin receptor (lepr). Conclusions: This study showed that high dietary PA\/(DHA + EPA) impacted glycolipid homeostasis through endocrine and transcriptional regulation, leading to increased crude lipid and decreased glycogen levels, which provides a theoretical basis for scientific aquatic feed fatty acid formulation.<\/jats:p>","DOI":"10.3390\/metabo16010072","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T11:42:58Z","timestamp":1768304578000},"page":"72","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["High Ratio of Dietary Palmitic Acid to DHA + EPA Induces Glucose Metabolic Disorder Through Endocrine and Transcriptional Regulation in Large Yellow Croaker (Larimichthys crocea)"],"prefix":"10.3390","volume":"16","author":[{"given":"Qi","family":"Wang","sequence":"first","affiliation":[{"name":"Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs) & Key Laboratory of Mariculture (Ministry of Education), Fisheries College, Ocean University of China, Qingdao 266003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huaicheng","family":"Ge","sequence":"additional","affiliation":[{"name":"Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs) & Key Laboratory of Mariculture (Ministry of Education), Fisheries College, Ocean University of China, Qingdao 266003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhixiang","family":"Gu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs) & Key Laboratory of Mariculture (Ministry of Education), Fisheries College, Ocean University of China, Qingdao 266003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs) & Key Laboratory of Mariculture (Ministry of Education), Fisheries College, Ocean University of China, Qingdao 266003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5585-4877","authenticated-orcid":false,"given":"Hua","family":"Mu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs) & Key Laboratory of Mariculture (Ministry of Education), Fisheries College, Ocean University of China, Qingdao 266003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kangsen","family":"Mai","sequence":"additional","affiliation":[{"name":"Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs) & Key Laboratory of Mariculture (Ministry of Education), Fisheries College, Ocean University of China, Qingdao 266003, China"},{"name":"Shenzhen Institute, Ocean University of China, Shenzhen 518100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenbing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs) & Key Laboratory of Mariculture (Ministry of Education), Fisheries College, Ocean University of China, Qingdao 266003, China"},{"name":"Shenzhen Institute, Ocean University of China, Shenzhen 518100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,13]]},"reference":[{"key":"ref_1","first-page":"13","article-title":"Fish meal and fish oil replacement for aqua feed formulation by using alternative sources: A review","volume":"23","author":"Hodar","year":"2020","journal-title":"J. Exp. Zool. India"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1111\/raq.12287","article-title":"Sustainable alternatives to dietary fish oil in tropical fish aquaculture","volume":"11","author":"Alhazzaa","year":"2019","journal-title":"Rev. Aquacult."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1111\/anu.12184","article-title":"Effects of fish oil replacement by a vegetable oil blend on digestibility, postprandial serum metabolite profile, lipid and glucose metabolism of E uropean sea bass (Dicentrarchus labrax) juveniles","volume":"21","author":"Castro","year":"2015","journal-title":"Aquac. Nutr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1007\/s10695-019-00646-1","article-title":"Comparative analysis of glucose metabolism responses of large yellow croaker Larimichthys crocea fed diet with fish oil and palm oil","volume":"45","author":"Wang","year":"2019","journal-title":"Fish Physiol. Biochem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"100756","DOI":"10.1016\/j.jhepr.2023.100756","article-title":"Saturated fatty acid-enriched small extracellular vesicles mediate a crosstalk inducing liver inflammation and hepatocyte insulin resistance","volume":"5","author":"Alen","year":"2023","journal-title":"JHEP Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e21712","DOI":"10.1096\/fj.202100243R","article-title":"Palmitic acid induces insulin resistance by a mechanism associated with energy metabolism and calcium entry in neuronal cells","volume":"35","author":"Vaca","year":"2021","journal-title":"FASEB J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"105802","DOI":"10.1016\/j.tiv.2024.105802","article-title":"Characterization of palmitic acid toxicity induced insulin resistance in HepG2 cells","volume":"97","author":"Malik","year":"2024","journal-title":"Toxicol. Vitr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2202976","DOI":"10.1080\/21623945.2023.2202976","article-title":"Adipokines in glucose and lipid metabolism","volume":"12","author":"Wang","year":"2023","journal-title":"Adipocyte"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/s41574-021-00471-8","article-title":"Lipid and glucose metabolism in white adipocytes: Pathways, dysfunction and therapeutics","volume":"17","author":"Morigny","year":"2021","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5236","DOI":"10.1021\/acs.jafc.4c09302","article-title":"HSF1 Mediates Palmitic Acid-Disrupted Lipid Metabolism and Inflammatory Response by Maintaining Endoplasmic Reticulum Homeostasis in Fish","volume":"73","author":"Jia","year":"2025","journal-title":"J. Agric. Food Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.fsi.2022.04.011","article-title":"Eicosapentaenoic acid mitigates palmitic acid-induced heat shock response, inflammation and repair processes in fish intestine","volume":"124","author":"Shi","year":"2022","journal-title":"Fish Shellfish Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4587907","DOI":"10.1155\/2022\/4587907","article-title":"The different insulin-sensitising and anti-inflammatory effects of palmitoleic acid and oleic acid in a prediabetes model","volume":"2022","author":"Miklankova","year":"2022","journal-title":"J. Diabetes Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1007\/s00360-012-0658-7","article-title":"Glucose metabolism in fish: A review","volume":"182","author":"Polakof","year":"2012","journal-title":"J. Comp. Physiol. B"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Poli, A., Agostoni, C., and Visioli, F. (2023). Dietary fatty acids and inflammation: Focus on the n-6 series. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24054567"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.2174\/1389200222666211126104002","article-title":"Regulatory effects of n-3 PUFAs on pancreatic \u03b2-cells and insulin-sensitive tissues","volume":"22","author":"Liu","year":"2021","journal-title":"Curr. Drug Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1007\/s10695-017-0353-4","article-title":"Effects of dietary n-3 fatty acids on Toll-like receptor activation in primary leucocytes from Atlantic salmon (Salmo salar)","volume":"43","author":"Arnemo","year":"2017","journal-title":"Fish Physiol. Biochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.aquaculture.2015.08.005","article-title":"N-3 essential fatty acids in Nile tilapia, Oreochromis niloticus: Effects of linolenic acid on non-specific immunity and anti-inflammatory responses in juvenile fish","volume":"450","author":"Chen","year":"2016","journal-title":"Aquaculture"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Russo, B., Menduni, M., Borboni, P., Picconi, F., and Frontoni, S. (2021). Autonomic nervous system in obesity and insulin-resistance\u2014The complex interplay between leptin and central nervous system. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22105187"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1530\/JOE-21-0139","article-title":"Evidence for a leptin\u2013insulin axis in a fish, the tilapia (Oreochromis mossambicus)","volume":"253","author":"Deck","year":"2022","journal-title":"J. Endocrinol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Balakrishnan, R., and Thurmond, D.C. (2022). Mechanisms by which skeletal muscle myokines ameliorate insulin resistance. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23094636"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5699931","DOI":"10.1155\/2022\/5699931","article-title":"Effects of adiponectin on glucose metabolism in the hepatopancreas of grass carp (Ctenopharyngodon idella)","volume":"2022","author":"Qin","year":"2022","journal-title":"Aquac. Nutr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"741026","DOI":"10.1016\/j.aquaculture.2024.741026","article-title":"Assessing the population genetic structure of yellow croaker in China: Insights into the ecological and genetic consequences of artificial breeding on natural populations","volume":"590","author":"Yuan","year":"2024","journal-title":"Aquaculture"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1139\/er-2020-0031","article-title":"Discrimination between freshwater and marine fish using fatty acids: Ecological implications and future perspectives","volume":"28","author":"Parzanini","year":"2020","journal-title":"Environ. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1577\/H06-044.1","article-title":"Comparison of chloroform\u2013methanol-extracted and solvent-free triglyceride determinations in four fish species","volume":"19","author":"Bennett","year":"2007","journal-title":"J. Aquat. Anim. Health"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.fsi.2018.04.017","article-title":"High level of dietary soybean oil depresses the growth and anti-oxidative capacity and induces inflammatory response in large yellow croaker Larimichthys crocea","volume":"77","author":"Mu","year":"2018","journal-title":"Fish Shellfish Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394CT method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_27","unstructured":"Wang, Q. (2019). Effects of Dietary Palmitic Acid and DHA\/EPA on Glucose Metabolism in Large Yellow Croaker (Larimichthys crocea). [Master\u2019s Thesis, Ocean University of China]."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"114504","DOI":"10.1016\/j.anifeedsci.2020.114504","article-title":"Partial replacement of fish oil with vegetal oils in commercial diets: The effect on the quality of gilthead seabream (Sparus aurata)","volume":"265","author":"Fontanillas","year":"2020","journal-title":"Anim. Feed Sci. Technol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1111\/raq.12905","article-title":"Modelling the impact of replacing fish oil with plant oils: A meta-analysis to match the optimal plant oil for major cultured fish","volume":"16","author":"Qian","year":"2024","journal-title":"Rev. Aquacult."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"736843","DOI":"10.1016\/j.aquaculture.2021.736843","article-title":"Different saturated and monounsaturated fatty acids levels in fish oil-free diets to cobia (Rachycentron canadum) juveniles: Effects in growth performance and lipid metabolism","volume":"541","author":"Marques","year":"2021","journal-title":"Aquaculture"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"739070","DOI":"10.1016\/j.aquaculture.2022.739070","article-title":"Fish oil replacement by beef tallow in juvenile turbot diets: Effects on growth performance, body composition and volatile flavor compounds in the muscle","volume":"564","author":"Zhang","year":"2023","journal-title":"Aquaculture"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Ramatchandirin, B., Pearah, A., and He, L. (2023). Regulation of liver glucose and lipid metabolism by transcriptional factors and coactivators. Life, 13.","DOI":"10.3390\/life13020515"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"100427","DOI":"10.1016\/j.aqrep.2020.100427","article-title":"Regulation of glucose and lipid metabolism by insulin and glucagon in vivo and in vitro in common carp Cyprinus carpio L.","volume":"18","author":"Yan","year":"2020","journal-title":"Aquac. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Egalini, F., Guardamagna, O., Gaggero, G., Varaldo, E., Giannone, B., Beccuti, G., Benso, A., and Broglio, F. (2023). The effects of omega 3 and omega 6 fatty acids on glucose metabolism: An updated review. Nutrients, 15.","DOI":"10.3390\/nu15122672"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.aquaculture.2006.07.018","article-title":"Dietary fat type affects lipid metabolism in Atlantic salmon (Salmo salar L.) and differentially regulates glucose transporter GLUT4 expression in muscle","volume":"261","author":"Menoyo","year":"2006","journal-title":"Aquaculture"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Li, X., Han, T., Zheng, S., and Wu, G. (2021). Hepatic glucose metabolism and its disorders in fish. Recent Advances in Animal Nutrition and Metabolism, Springer.","DOI":"10.1007\/978-3-030-85686-1_11"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.cbpb.2018.12.003","article-title":"High level of dietary soybean oil affects the glucose and lipid metabolism in large yellow croaker Larimichthys crocea through the insulin-mediated PI3K\/AKT signaling pathway","volume":"231","author":"Gu","year":"2019","journal-title":"Comp. Biochem. Phys. B"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1007\/s10695-023-01285-3","article-title":"The preferential utilization of hepatic glycogen as energy substrates in largemouth bass (Micropterus salmoides) under short-term starvation","volume":"50","author":"Zhang","year":"2024","journal-title":"Fish Physiol. Biochem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.aaf.2017.02.001","article-title":"Growth performance, feed utilization, body and fatty acid composition of Nile tilapia (Oreochromis niloticus) fed diets containing elevated levels of palm oil","volume":"2","author":"Ayisi","year":"2017","journal-title":"Aquac. Fish."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.fsi.2019.02.055","article-title":"Berberine attenuates sodium palmitate-induced lipid accumulation, oxidative stress and apoptosis in grass carp (Ctenopharyngodon idella) hepatocyte in vitro","volume":"88","author":"Yang","year":"2019","journal-title":"Fish Shellfish Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1111\/are.15651","article-title":"Effects of sodium acetate on lipid metabolism, antioxidant capability and cell apoptosis of blunt snout bream (Megalobrama amblycephala) hepatocytes treated by sodium palmitate","volume":"53","author":"Yu","year":"2022","journal-title":"Aquac. Res."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Mzengereza, K., Ishikawa, M., Koshio, S., Yokoyama, S., Yukun, Z., Shadrack, R.S., Seo, S., Duy Khoa, T.N., Moss, A., and Dossou, S. (2021). Effect of substituting fish oil with camelina oil on growth performance, fatty acid profile, digestibility, liver histology, and antioxidative status of red seabream (Pagrus major). Animals, 11.","DOI":"10.3390\/ani11071990"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/anu.13174","article-title":"Effects of dietary fish oil replacements with three vegetable oils on growth, fatty acid composition, antioxidant capacity, serum parameters and expression of lipid metabolism related genes in juvenile Onychostoma macrolepis","volume":"27","author":"Gou","year":"2021","journal-title":"Aquac. Nutr."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.1007\/s12035-022-02756-z","article-title":"Palmitic acid and oleic acid differently modulate TLR2-mediated inflammatory responses in microglia and macrophages","volume":"59","author":"Howe","year":"2022","journal-title":"Mol. Neurobiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/s41392-025-02295-8","article-title":"Oleic acid restores the impaired antitumor immunity of \u03b3\u03b4-T cells induced by palmitic acid","volume":"10","author":"Zhang","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s10695-019-00712-8","article-title":"Impacts of replacement of dietary fish oil by vegetable oils on growth performance, anti-oxidative capacity, and inflammatory response in large yellow croaker Larimichthys crocea","volume":"46","author":"Mu","year":"2020","journal-title":"Fish Physiol. Biochem."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Shi, J., Fan, J., Su, Q., and Yang, Z. (2019). Cytokines and abnormal glucose and lipid metabolism. Front. Endocrinol., 10.","DOI":"10.3389\/fendo.2019.00703"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/nri2921","article-title":"Adipokines in inflammation and metabolic disease","volume":"11","author":"Ouchi","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Song, Y.-F., Tan, X.-Y., Pan, Y.-X., Zhang, L.-H., and Chen, Q.-L. (2018). Fatty acid \u03b2-oxidation is essential in leptin-mediated oocytes maturation of yellow catfish Pelteobagrus fulvidraco. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19051457"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s11154-021-09687-5","article-title":"Leptin as a key regulator of the adipose organ","volume":"23","author":"Palou","year":"2022","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1002\/hep.20821","article-title":"Role of adiponectin in the protective action of dietary saturated fat against alcoholic fatty liver in mice","volume":"42","author":"You","year":"2005","journal-title":"Hepatology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.1111\/raq.12569","article-title":"Adiponectin\u2019s roles in lipid and glucose metabolism modulation in fish: Mechanisms and perspectives","volume":"13","author":"Ji","year":"2021","journal-title":"Rev. Aquacult."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"183","DOI":"10.2337\/diaspect.17.3.183","article-title":"Glucose metabolism and regulation: Beyond insulin and glucagon","volume":"17","author":"Aronoff","year":"2004","journal-title":"Diabetes Spectr."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Gupta, R., and Gupta, N. (2021). Glycolysis and gluconeogenesis. Fundamentals of Bacterial Physiology and Metabolism, Springer.","DOI":"10.1007\/978-981-16-0723-3"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3538","DOI":"10.1021\/acs.jmedchem.9b01851","article-title":"Discovery and development of small-molecule inhibitors of glycogen synthase","volume":"63","author":"Tang","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e202309090","DOI":"10.1083\/jcb.202309090","article-title":"Tip60-mediated Rheb acetylation links palmitic acid with mTORC1 activation and insulin resistance","volume":"223","author":"Zhao","year":"2024","journal-title":"J. Cell Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"553","DOI":"10.7150\/ijbs.40643","article-title":"The role of Akt2 in the protective effect of fenofibrate against diabetic nephropathy","volume":"16","author":"Cheng","year":"2020","journal-title":"Int. J. Biol. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1159\/000453174","article-title":"The crucial role of C18-Cer in fat-induced skeletal muscle insulin resistance","volume":"40","author":"Chacinska","year":"2016","journal-title":"Cell. Physiol. Biochem."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/16\/1\/72\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T06:00:13Z","timestamp":1768456813000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/16\/1\/72"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,13]]},"references-count":58,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["metabo16010072"],"URL":"https:\/\/doi.org\/10.3390\/metabo16010072","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,13]]}}}