{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T10:20:26Z","timestamp":1780568426552,"version":"3.54.1"},"reference-count":45,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,15]],"date-time":"2022-01-15T00:00:00Z","timestamp":1642204800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81973031"],"award-info":[{"award-number":["81973031"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82003447"],"award-info":[{"award-number":["82003447"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81803224"],"award-info":[{"award-number":["81803224"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Cheeloo Young Scholar Program of Shandong University","award":["21320089963054"],"award-info":[{"award-number":["21320089963054"]}]},{"name":"Young Scholars Program of Shandong University","award":["2018WLJH34"],"award-info":[{"award-number":["2018WLJH34"]}]},{"name":"Young Scholars Program of Shandong University","award":["2018WLJH33"],"award-info":[{"award-number":["2018WLJH33"]}]},{"name":"the Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology","award":["LMDBKF-2019-05"],"award-info":[{"award-number":["LMDBKF-2019-05"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Diabetic cardiomyopathy (DCM) is a common complication of diabetes mellitus (DM), resulting in high mortality. Myocardial fibrosis, cardiomyocyte apoptosis and inflammatory cell infiltration are hallmarks of DCM, leading to cardiac dysfunction. To date, few effective approaches have been developed for the intervention of DCM. In the present study, we investigate the effect of krill oil (KO) on the prevention of DCM using a mouse model of DM induced by streptozotocin and a high-fat diet. The diabetic mice developed pathological features, including cardiac fibrosis, apoptosis and inflammatory cell infiltration, the effects of which were remarkably prevented by KO. Mechanistically, KO reversed the DM-induced cardiac expression of profibrotic and proinflammatory genes and attenuated DM-enhanced cardiac oxidative stress. Notably, KO exhibited a potent inhibitory effect on NLR family pyrin domain containing 3 (NLRP3) inflammasome that plays an important role in DCM. Further investigation showed that KO significantly upregulated the expression of Sirtuin 3 (SIRT3) and peroxisome proliferator-activated receptor-\u03b3 coactivator 1\u03b1 (PGC-1\u03b1), which are negative regulators of NLRP3. The present study reports for the first time the preventive effect of KO on the pathological injuries of DCM, providing SIRT3, PGC-1\u03b1 and NLRP3 as molecular targets of KO. This work suggests that KO supplementation may be a viable approach in clinical prevention of DCM.<\/jats:p>","DOI":"10.3390\/nu14020368","type":"journal-article","created":{"date-parts":[[2022,1,16]],"date-time":"2022-01-16T20:45:21Z","timestamp":1642365921000},"page":"368","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Krill Oil Inhibits NLRP3 Inflammasome Activation in the Prevention of the Pathological Injuries of Diabetic Cardiomyopathy"],"prefix":"10.3390","volume":"14","author":[{"given":"Xuechun","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Cheeloo College of Medicine, Shandong University, 44 Wenhuaxi Rd., Jinan 250012, China"},{"name":"Research Center of Translational Medicine, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, 105 Jiefang Rd., Jinan 250013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodan","family":"Sun","sequence":"additional","affiliation":[{"name":"Intensive Care Unit, The Second Hospital, Cheeloo College of Medicine, Shandong University, 247 Beiyuan Rd., Jinan 250033, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huali","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Cheeloo College of Medicine, Shandong University, 44 Wenhuaxi Rd., Jinan 250012, China"},{"name":"Research Center of Translational Medicine, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, 105 Jiefang Rd., Jinan 250013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junduo","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Second Hospital of Jilin University, 218 Ziqiang St., Changchun 130041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Cheeloo College of Medicine, Shandong University, 44 Wenhuaxi Rd., Jinan 250012, China"},{"name":"Research Center of Translational Medicine, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, 105 Jiefang Rd., Jinan 250013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8173-5575","authenticated-orcid":false,"given":"Lei","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Cheeloo College of Medicine, Shandong University, 44 Wenhuaxi Rd., Jinan 250012, China"},{"name":"Research Center of Translational Medicine, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, 105 Jiefang Rd., Jinan 250013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Cheeloo College of Medicine, Shandong University, 44 Wenhuaxi Rd., Jinan 250012, China"},{"name":"Research Center of Translational Medicine, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, 105 Jiefang Rd., Jinan 250013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"107843","DOI":"10.1016\/j.diabres.2019.107843","article-title":"Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9(th) edition","volume":"157","author":"Saeedi","year":"2019","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.pharmthera.2014.01.003","article-title":"Diabetic cardiomyopathy: Mechanisms and new treatment strategies targeting antioxidant signaling pathways","volume":"142","author":"Huynh","year":"2014","journal-title":"Pharmacol. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.mayocp.2019.07.008","article-title":"Diabetes Mellitus Is an Independent Predictor for the Development of Heart Failure: A Population Study","volume":"95","author":"Klajda","year":"2020","journal-title":"Mayo Clin. Proc."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1042\/CS20160491","article-title":"Are targeted therapies for diabetic cardiomyopathy on the horizon?","volume":"131","author":"Tate","year":"2017","journal-title":"Clin. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1161\/CIRCRESAHA.120.315913","article-title":"Basic Mechanisms of Diabetic Heart Disease","volume":"126","author":"Ritchie","year":"2020","journal-title":"Circ. Res."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Zaloga, G.P. (2021). Narrative Review of n-3 Polyunsaturated Fatty Acid Supplementation upon Immune Functions, Resolution Molecules and Lipid Peroxidation. Nutrients, 13.","DOI":"10.3390\/nu13020662"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"110306","DOI":"10.1016\/j.biopha.2020.110306","article-title":"Docosahexaenoic acid protects against palmitate-induced mitochondrial dysfunction in diabetic cardiomyopathy","volume":"128","author":"Gui","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3300","DOI":"10.3390\/nu7053300","article-title":"Krill products: An overview of animal studies","volume":"7","author":"Burri","year":"2015","journal-title":"Nutrients"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1021\/acs.jafc.9b07370","article-title":"Real-Time Monitoring of the Oxidation Characteristics of Antarctic Krill Oil (Euphausia superba) during Storage by Electric Soldering Iron Ionization Mass Spectrometry-Based Lipidomics","volume":"68","author":"Song","year":"2020","journal-title":"J. Agric. Food Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1194\/jlr.M045930","article-title":"Higher efficacy of dietary DHA provided as a phospholipid than as a triglyceride for brain DHA accretion in neonatal piglets","volume":"55","author":"Liu","year":"2014","journal-title":"J. Lipid Res."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Landon, R., Gueguen, V., Petite, H., Letourneur, D., Pavon-Djavid, G., and Anagnostou, F. (2020). Impact of Astaxanthin on Diabetes Pathogenesis and Chronic Complications. Mar. Drugs, 18.","DOI":"10.3390\/md18070357"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1016\/j.bbamcr.2018.04.011","article-title":"MDM2 controls NRF2 antioxidant activity in prevention of diabetic kidney disease","volume":"1865","author":"Guo","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1007\/s00125-016-3958-8","article-title":"C66 ameliorates diabetic nephropathy in mice by both upregulating NRF2 function via increase in miR-200a and inhibiting miR-21","volume":"59","author":"Wu","year":"2016","journal-title":"Diabetologia"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1096\/fj.07-9574LSF","article-title":"Dose translation from animal to human studies revisited","volume":"22","author":"Nihal","year":"2008","journal-title":"FASEB J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.toxlet.2014.11.015","article-title":"Metallothionein deletion exacerbates intermittent hypoxia-induced renal injury in mice","volume":"232","author":"Wu","year":"2015","journal-title":"Toxicol. Lett."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Kelley, N., Jeltema, D., Duan, Y., and He, Y. (2019). The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133328"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1023\/B:MCBI.0000028755.86521.11","article-title":"Molecular and cellular basis of the aetiology and management of diabetic cardiomyopathy: A short review","volume":"261","author":"Adeghate","year":"2004","journal-title":"Mol. Cell. Biochem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.jacc.2005.09.050","article-title":"The pathogenesis of myocardial fibrosis in the setting of diabetic cardiomyopathy","volume":"47","author":"Asbun","year":"2006","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Jubaidi, F.F., Zainalabidin, S., Taib, I.S., Hamid, Z.A., and Budin, S.B. (2021). The Potential Role of Flavonoids in Ameliorating Diabetic Cardiomyopathy via Alleviation of Cardiac Oxidative Stress, Inflammation and Apoptosis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22105094"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.bbadis.2014.06.030","article-title":"Interplay of oxidative, nitrosative\/nitrative stress, inflammation, cell death and autophagy in diabetic cardiomyopathy","volume":"1852","author":"Varga","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"694864","DOI":"10.3389\/fphys.2021.694864","article-title":"Mechanisms and Therapeutic Prospects of Diabetic Cardiomyopathy Through the Inflammatory Response","volume":"12","author":"Kaur","year":"2021","journal-title":"Front. Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nm.2279","article-title":"The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance","volume":"17","author":"Vandanmagsar","year":"2011","journal-title":"Nat. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4437","DOI":"10.1111\/jcmm.13743","article-title":"Gypenosides improve diabetic cardiomyopathy by inhibiting ROS-mediated NLRP3 inflammasome activation","volume":"22","author":"Zhang","year":"2018","journal-title":"J. Cell. Mol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1007\/s00395-019-0771-9","article-title":"Thrombin receptor PAR4 drives canonical NLRP3 inflammasome signaling in the heart","volume":"115","author":"Fender","year":"2020","journal-title":"Basic Res. Cardiol."},{"key":"ref_25","first-page":"5282","article-title":"Melatonin alleviates cardiac fibrosis via inhibiting lncRNA MALAT1\/miR-141-mediated NLRP3 inflammasome and TGF-\u03b21\/Smads signaling in diabetic cardiomyopathy","volume":"34","author":"Che","year":"2020","journal-title":"FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s10557-013-6498-1","article-title":"Rosuvastatin alleviates diabetic cardiomyopathy by inhibiting NLRP3 inflammasome and MAPK pathways in a type 2 diabetes rat model","volume":"28","author":"Luo","year":"2014","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1016\/j.bbrc.2017.09.151","article-title":"Polydatin ameliorates diabetic cardiomyopathy via Sirt3 activation","volume":"493","author":"Zhang","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_28","first-page":"10872","article-title":"The nuclear and mitochondrial sirtuins, Sirt6 and Sirt3, regulate each other\u2019s activity and protect the heart from developing obesity-mediated diabetic cardiomyopathy","volume":"33","author":"Kanwal","year":"2019","journal-title":"FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"256","DOI":"10.3389\/fphar.2020.00256","article-title":"Icariin Ameliorates Diabetic Cardiomyopathy Through Apelin\/Sirt3 Signalling to Improve Mitochondrial Dysfunction","volume":"11","author":"Ni","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4203","DOI":"10.1093\/nar\/gkab161","article-title":"SIRT3 consolidates heterochromatin and counteracts senescence","volume":"49","author":"Diao","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4579","DOI":"10.1002\/ptr.7175","article-title":"Salidroside protects cardiac function in mice with diabetic cardiomyopathy via activation of mitochondrial biogenesis and SIRT3","volume":"35","author":"Li","year":"2021","journal-title":"Phytother. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"254","DOI":"10.7150\/ijbs.17053","article-title":"Sirtuin 3 is required for osteogenic differentiation through maintenance of PGC-1a-SOD2-mediated regulation of mitochondrial function","volume":"13","author":"Ding","year":"2017","journal-title":"Int. J. Biol. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1152\/advan.00052.2006","article-title":"PGC-1alpha: A key regulator of energy metabolism","volume":"30","author":"Liang","year":"2006","journal-title":"Adv. Physiol. Educ."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Kong, X., Wang, R., Xue, Y., Liu, X., Zhang, H., Chen, Y., Fang, F., and Chang, Y. (2010). Sirtuin 3, a new target of PGC-1alpha, plays an important role in the suppression of ROS and mitochondrial biogenesis. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0011707"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e05159","DOI":"10.1016\/j.heliyon.2020.e05159","article-title":"Activation of SIRT1\/PGC 1\u03b1\/SIRT3 pathway by melatonin provides protection against mitochondrial dysfunction in isoproterenol induced myocardial injury","volume":"6","author":"Naaz","year":"2020","journal-title":"Heliyon"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/aps.2017.50","article-title":"Resveratrol alleviates diabetic cardiomyopathy in rats by improving mitochondrial function through PGC-1\u03b1 deacetylation","volume":"39","author":"Fang","year":"2018","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_37","first-page":"233","article-title":"CYP-450 Epoxygenase Derived Epoxyeicosatrienoic Acid Contribute To Reversal of Heart Failure in Obesity-Induced Diabetic Cardiomyopathy via PGC-1 \u03b1 Activation","volume":"7","author":"Singh","year":"2018","journal-title":"Cardiovasc. Pharmacol. Open Access"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1159\/000374021","article-title":"Exercise Prevents Cardiac Injury and Improves Mitochondrial Biogenesis in Advanced Diabetic Cardiomyopathy with PGC-1\u03b1 and Akt Activation","volume":"35","author":"Wang","year":"2015","journal-title":"Cell. Physiol. Biochem. Int. J. Exp. Cell. Physiol. Biochem. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.dld.2019.09.002","article-title":"L-carnitine supplementation attenuates NAFLD progression and cardiac dysfunction in a mouse model fed with methionine and choline-deficient diet","volume":"52","author":"Mollica","year":"2020","journal-title":"Dig. Liver Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e312","DOI":"10.1002\/ctm2.312","article-title":"Vitamin D3 ameliorates nitrogen mustard-induced cutaneous inflammation by inactivating the NLRP3 inflammasome through the SIRT3-SOD2-mtROS signaling pathway","volume":"11","author":"Dong","year":"2021","journal-title":"Clin. Transl. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"12153","DOI":"10.1074\/jbc.M117.791715","article-title":"Prolonged fasting suppresses mitochondrial NLRP3 inflammasome assembly and activation via SIRT3-mediated activation of superoxide dismutase 2","volume":"292","author":"Traba","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"13609","DOI":"10.1111\/jcmm.15663","article-title":"Tris DBA ameliorates IgA nephropathy by blunting the activating signal of NLRP3 inflammasome through SIRT1- and SIRT3-mediated autophagy induction","volume":"24","author":"Wu","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"577062","DOI":"10.3389\/fphar.2020.577062","article-title":"\u03b1-Cyperone Confers Antidepressant-Like Effects in Mice via Neuroplasticity Enhancement by SIRT3\/ROS Mediated NLRP3 Inflammasome Deactivation","volume":"11","author":"Xia","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"511","DOI":"10.2147\/VHRM.S85165","article-title":"Comparison of bioavailability of krill oil versus fish oil and health effect","volume":"11","author":"Ulven","year":"2015","journal-title":"Vasc. Health Risk Manag."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.5650\/jos.ess18086","article-title":"Effect of Hazelnut Oil on Muscle Cell Signalling and Differentiation","volume":"67","author":"Terruzzi","year":"2018","journal-title":"J. Oleo Sci."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/2\/368\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:39:54Z","timestamp":1760362794000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/2\/368"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,15]]},"references-count":45,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["nu14020368"],"URL":"https:\/\/doi.org\/10.3390\/nu14020368","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,15]]}}}