{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T05:45:42Z","timestamp":1782539142911,"version":"3.54.5"},"reference-count":44,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100022963","name":"Key R&D Program of Zhejiang Province","doi-asserted-by":"crossref","award":["2025C01100"],"award-info":[{"award-number":["2025C01100"]}],"id":[{"id":"10.13039\/100022963","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100022963","name":"Key R&D Program of Zhejiang Province","doi-asserted-by":"crossref","award":["2025C02088"],"award-info":[{"award-number":["2025C02088"]}],"id":[{"id":"10.13039\/100022963","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Key Science and Technology Project of Marine Industry of Zhejiang Province","award":["2026HYB01004"],"award-info":[{"award-number":["2026HYB01004"]}]},{"name":"Taizhou Municipal Science and Technology Program","award":["25nyb07"],"award-info":[{"award-number":["25nyb07"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Obesity-associated metabolic dysfunction involves oxidative stress, gut barrier impairment, and gut\u2013liver axis disruption. This study evaluated whether enzymatically prepared Solenocera crassicornis peptides (SCPs) provide additional benefits during diet normalization in HFD-induced obese mice and examined associations with antioxidant, microbial, and barrier markers. Methods: SCPs were characterized using UPLC-Q-TOF-MS\/MS and amino acid analysis. Peptides underwent bioactivity prediction and Keap1 docking. After 7 weeks of HFD feeding, obese male C57BL\/6J mice were switched to a normal diet and administered vehicle, orlistat, or SCPs for 4 weeks. Adipose tissue mass, serum lipid profiles, liver histology, hepatic antioxidant status, barrier-associated histological and biochemical markers, and gut microbiota composition were assessed. A simulated digestion\u2013fecal fermentation model was used to assess the effects of fermentation products generated in the presence of digested SCPs on H2O2-induced oxidative injury and MUC2 secretion in LS174T goblet-like cells. Results: SCPs reduced epididymal and perirenal fat, improved serum lipids, improved hepatic steatosis-related morphology and enhanced hepatic antioxidant status. SCPs were also associated with improved intestinal morphology, increased mucin-associated staining, decreased serum diamine oxidase levels and reduced hepatic lipopolysaccharide accumulation. 16S rRNA sequencing showed SCP-associated microbial shifts, with correlations linking taxa to metabolic and barrier markers. Fermentation products generated in the presence of digested SCPs improved oxidative-stress and MUC2-related readouts in LS174T cells. Conclusions: During diet normalization, SCPs were associated with additional improvements in adiposity, lipid profiles, hepatic antioxidant status, intestinal barrier readouts, and gut microbiota. These findings support further investigation of SCPs as standardized marine protein hydrolysates, but active components, causal mechanisms, long-term efficacy, safety, and human relevance remain to be established.<\/jats:p>","DOI":"10.3390\/nu18122029","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T06:13:37Z","timestamp":1782195217000},"page":"2029","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Marine Peptides from Solenocera crassicornis Are Associated with Improved Metabolic, Hepatic, and Intestinal Markers During Diet Normalization in HFD-Induced Obese Mice"],"prefix":"10.3390","volume":"18","author":[{"given":"Huirong","family":"Lv","sequence":"first","affiliation":[{"name":"Xianghu Laboratory, Hangzhou 311231, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Food Science and Pharmaceutics, Zhejiang Ocean University, Zhoushan 316022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongcang","family":"Qian","sequence":"additional","affiliation":[{"name":"Institute of Ecological and Environmental Sciences, Taizhou Academy of Agricultural Sciences, Taizhou 318099, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gen","family":"Lin","sequence":"additional","affiliation":[{"name":"Hangzhou Nutrition Biotechnology Co., Ltd., Hangzhou 311200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengshun","family":"Wen","sequence":"additional","affiliation":[{"name":"Xianghu Laboratory, Hangzhou 311231, China"},{"name":"School of Food Science and Pharmaceutics, Zhejiang Ocean University, Zhoushan 316022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1038\/s41574-019-0176-8","article-title":"Obesity: Global epidemiology and pathogenesis","volume":"15","year":"2019","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Fahed, G., Aoun, L., Bou Zerdan, M., Allam, S., Bou Zerdan, M., Bouferraa, Y., and Assi, H.I. (2022). Metabolic syndrome: Updates on pathophysiology and management in 2021. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23020786"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ma, K., Zhang, Y., Zhao, J., Zhou, L., and Li, M. (2024). Endoplasmic reticulum stress: Bridging inflammation and obesity-associated adipose tissue. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1381227"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"95","DOI":"10.3892\/mmr.2024.13219","article-title":"Molecular and pathophysiological relationship between obesity and chronic inflammation in the manifestation of metabolic dysfunctions and their inflammation-mediating treatment options","volume":"29","author":"Varra","year":"2024","journal-title":"Mol. Med. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1210\/jc.2014-3415","article-title":"Pharmacological management of obesity: An Endocrine Society clinical practice guideline","volume":"100","author":"Apovian","year":"2015","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.biopha.2017.06.035","article-title":"Antiobesity, antioxidant and hepatoprotective effects of Diallyl trisulphide (DATS) alone or in combination with Orlistat on HFD induced obese rats","volume":"93","author":"Annamalai","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5039","DOI":"10.1080\/10408398.2022.2148090","article-title":"Shared signaling pathways and targeted therapy by natural bioactive compounds for obesity and type 2 diabetes","volume":"64","author":"Tian","year":"2024","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"8425","DOI":"10.1080\/10408398.2025.2500675","article-title":"Food-derived polysaccharides and anti-obesity effects through enhancing adipose thermogenesis: Structure-activity relationships, mechanisms, and regulation of gut microecology","volume":"65","author":"Wang","year":"2025","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"11401","DOI":"10.1021\/acs.jafc.2c04406","article-title":"Phytic acid improves hepatic steatosis, inflammation, and oxidative stress in high-fat diet (HFD)-fed mice by modulating the gut-liver axis","volume":"70","author":"Ran","year":"2022","journal-title":"J. Agric. Food Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1002\/biof.2028","article-title":"High-fat diet induced obesity promotes inflammation, oxidative stress, and hepatotoxicity in female FVB\/N mice","volume":"50","author":"Shaik","year":"2024","journal-title":"Biofactors"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1080\/10408398.2025.2556470","article-title":"Targeting the gut-liver axis with dietary polyphenols to ameliorate metabolic dysfunction-associated steatotic liver disease: Advances in molecular mechanisms","volume":"66","author":"Hu","year":"2025","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"20220210","DOI":"10.1098\/rstb.2022.0210","article-title":"Reactive oxygen species: Role in obesity and mitochondrial energy efficiency","volume":"378","author":"Corkey","year":"2023","journal-title":"Philos. Trans. R. Soc. B"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Zheng, Z., and Wang, B. (2021). The gut-liver axis in health and disease: The role of gut microbiota-derived signals in liver injury and regeneration. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.775526"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1016\/j.cmet.2022.09.017","article-title":"Gut-liver axis: Pathophysiological concepts and clinical implications","volume":"34","author":"Tilg","year":"2022","journal-title":"Cell Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.cofs.2014.12.009","article-title":"Novel functional food ingredients from marine sources","volume":"2","author":"Shahidi","year":"2015","journal-title":"Curr. Opin. Food Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8905","DOI":"10.1080\/10408398.2025.2513517","article-title":"Comprehensive exploration of marine functional foods in modulation of metabolic syndromes: A 20-year review","volume":"65","author":"Amanat","year":"2025","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Zhu, Y., Lao, F., Pan, X., and Wu, J. (2022). Food protein-derived antioxidant peptides: Molecular mechanism, stability and bioavailability. Biomolecules, 12.","DOI":"10.3390\/biom12111622"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Jiang, S., Zhang, Z., Huang, F., Yang, Z., Yu, F., Tang, Y., and Ding, G. (2020). Protective effect of low molecular weight peptides from Solenocera crassicornis head against cyclophosphamide-induced nephrotoxicity in mice via the Keap1\/Nrf2 pathway. Antioxidants, 9.","DOI":"10.3390\/antiox9080745"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"104085","DOI":"10.1016\/j.jff.2020.104085","article-title":"Ameliorative effect of low molecular weight peptides from the head of red shrimp (Solenocera crassicornis) against cyclophosphamide-induced hepatotoxicity in mice","volume":"72","author":"Jiang","year":"2020","journal-title":"J. Funct. Foods"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Wang, Q., Wang, Y., Jiang, X., Ma, L., Li, Z., Chang, Y., Wang, Y., and Xue, C. (2021). Amino acid profiling with chemometric analysis as a feasible tool for the discrimination of marine-derived peptide powders. Foods, 10.","DOI":"10.3390\/foods10061294"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Lu, N., Wu, L., Zhen, S., and Liu, B. (2023). Characterization of a dihydromyricetin\/\u03b1-lactoalbumin covalent complex and its application in nano-emulsions. Foods, 12.","DOI":"10.3390\/foods12142783"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1007\/BF00702340","article-title":"The human intestinal cell lines Caco-2 and LS174T as models to study cell-type specific mucin expression","volume":"13","author":"Oussoren","year":"1996","journal-title":"Glycoconj. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J. Immunol. Methods"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/nmeth.f.303","article-title":"QIIME allows analysis of high-throughput community sequencing data","volume":"7","author":"Caporaso","year":"2010","journal-title":"Nat. Methods"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5261","DOI":"10.1128\/AEM.00062-07","article-title":"Naive Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy","volume":"73","author":"Wang","year":"2007","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"D590","DOI":"10.1093\/nar\/gks1219","article-title":"The SILVA ribosomal RNA gene database project: Improved data processing and web-based tools","volume":"41","author":"Quast","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1039\/C3FO60702J","article-title":"A standardised static in vitro digestion method suitable for food\u2014An international consensus","volume":"5","author":"Minekus","year":"2014","journal-title":"Food Funct."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Mooney, C., Haslam, N.J., Pollastri, G., and Shields, D.C. (2012). Towards the improved discovery and design of functional peptides: Common features of diverse classes permit generalized prediction of bioactivity. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0045012"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"21471","DOI":"10.1038\/s41598-020-78319-w","article-title":"AnOxPePred: Using deep learning for the prediction of antioxidative properties of peptides","volume":"10","author":"Olsen","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Gupta, S., Kapoor, P., Chaudhary, K., Gautam, A., Kumar, R., and Raghava, G.P. (2013). In silico approach for predicting toxicity of peptides and proteins. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0073957"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Minkiewicz, P., Iwaniak, A., and Darewicz, M. (2019). BIOPEP-UWM database of bioactive peptides: Current opportunities. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20235978"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.1002\/jcc.21256","article-title":"AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility","volume":"30","author":"Morris","year":"2009","journal-title":"J. Comput. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1016\/j.peptides.2010.06.020","article-title":"Antioxidative peptides from food proteins: A review","volume":"31","author":"Sarmadi","year":"2010","journal-title":"Peptides"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"103696","DOI":"10.1016\/j.jff.2019.103696","article-title":"Milk-derived bioactive peptides exhibit antioxidant activity through the Keap1-Nrf2 signaling pathway","volume":"64","author":"Tonolo","year":"2020","journal-title":"J. Funct. Foods"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Zhao, F., Ci, X., Man, X., Li, J., Wei, Z., and Zhang, S. (2021). Food-derived pharmacological modulators of the Nrf2\/ARE pathway: Their role in the treatment of diseases. Molecules, 26.","DOI":"10.3390\/molecules26041016"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Gao, M., Ma, Y., and Liu, D. (2015). High-fat diet-induced adiposity, adipose inflammation, hepatic steatosis and hyperinsulinemia in outbred CD-1 mice. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0119784"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Wang, Y.F., Wang, S., Xu, H.Y., and Liu, L.J. (2022). Commentary: Intestinal barrier function and immune homeostasis are missing links in obesity and type 2 diabetes development. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.939703"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1007\/s00018-012-1070-x","article-title":"Regulation of intestinal epithelial permeability by tight junctions","volume":"70","author":"Suzuki","year":"2013","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1007\/s43393-021-00035-x","article-title":"The alteration of gut microbiota by bioactive peptides: A review","volume":"1","author":"Guo","year":"2021","journal-title":"Syst. Microbiol. Biomanufacturing"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2190300","DOI":"10.1080\/19490976.2023.2190300","article-title":"Succinate metabolism and its regulation of host-microbe interactions","volume":"15","author":"Wei","year":"2023","journal-title":"Gut Microbes"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"skab346","DOI":"10.1093\/jas\/skab346","article-title":"Considerations and best practices in animal science 16S ribosomal RNA gene sequencing microbiome studies","volume":"100","author":"Weinroth","year":"2022","journal-title":"J. Anim. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1941711","DOI":"10.1080\/19490976.2021.1941711","article-title":"Investigating causality with fecal microbiota transplantation in rodents: Applications, recommendations and pitfalls","volume":"13","author":"Gheorghe","year":"2021","journal-title":"Gut Microbes"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1042\/BJ20082222","article-title":"The regulation of intestinal mucin MUC2 expression by short-chain fatty acids: Implications for epithelial protection","volume":"420","author":"Vincent","year":"2009","journal-title":"Biochem. J."},{"key":"ref_44","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."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/12\/2029\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T04:54:00Z","timestamp":1782536040000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/12\/2029"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,22]]},"references-count":44,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["nu18122029"],"URL":"https:\/\/doi.org\/10.3390\/nu18122029","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,22]]}}}