{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T19:07:23Z","timestamp":1785006443824,"version":"3.55.0"},"reference-count":72,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,18]],"date-time":"2021-08-18T00:00:00Z","timestamp":1629244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["435005007"],"award-info":[{"award-number":["435005007"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>The development of obesity is characterized by the metabolic overload of tissues and subsequent organ inflammation. The health effects of krill oil (KrO) on obesity-associated inflammation remain largely elusive, because long-term treatments with KrO have not been performed to date. Therefore, we examined the putative health effects of 28 weeks of 3% (w\/w) KrO supplementation to an obesogenic diet (HFD) with fat derived mostly from lard. The HFD with KrO was compared to an HFD control group to evaluate the effects on fatty acid composition and associated inflammation in epididymal white adipose tissue (eWAT) and the liver during obesity development. KrO treatment increased the concentrations of EPA and DHA and associated oxylipins, including 18-HEPE, RvE2 and 14-HDHA in eWAT and the liver. Simultaneously, KrO decreased arachidonic acid concentrations and arachidonic-acid-derived oxylipins (e.g., HETEs, PGD2, PGE2, PGF2\u03b1, TXB2). In eWAT, KrO activated regulators of adipogenesis (e.g., PPAR\u03b3, CEBP\u03b1, KLF15, STAT5A), induced a shift towards smaller adipocytes and increased the total adipocyte numbers indicative for hyperplasia. KrO reduced crown-like structures in eWAT, and suppressed HFD-stimulated inflammatory pathways including TNF\u03b1 and CCL2\/MCP-1 signaling. The observed eWAT changes were accompanied by reduced plasma leptin and increased plasma adiponectin levels over time, and improved insulin resistance (HOMA-IR). In the liver, KrO suppressed inflammatory signaling pathways, including those controlled by IL-1\u03b2 and M-CSF, without affecting liver histology. Furthermore, KrO deactivated hepatic REL-A\/p65-NF-\u03baB signaling, consistent with increased PPAR\u03b1 protein expression and a trend towards an increase in IkB\u03b1. In conclusion, long-term KrO treatment increased several anti-inflammatory PUFAs and oxylipins in WAT and the liver. These changes were accompanied by beneficial effects on general metabolism and inflammatory tone at the tissue level. The stimulation of adipogenesis by KrO allows for safe fat storage and may, together with more direct PPAR-mediated anti-inflammatory mechanisms, attenuate inflammation.<\/jats:p>","DOI":"10.3390\/nu13082836","type":"journal-article","created":{"date-parts":[[2021,8,18]],"date-time":"2021-08-18T10:54:35Z","timestamp":1629284075000},"page":"2836","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Krill Oil Treatment Increases Distinct PUFAs and Oxylipins in Adipose Tissue and Liver and Attenuates Obesity-Associated Inflammation via Direct and Indirect Mechanisms"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7713-2381","authenticated-orcid":false,"given":"Eveline","family":"Gart","sequence":"first","affiliation":[{"name":"Department of Metabolic Health Research, The Netherlands Organisation for Applied Scientific Research (TNO), 2333 CK Leiden, The Netherlands"},{"name":"Human and Animal Physiology, Wageningen University, 6708 WD Wageningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanita","family":"Salic","sequence":"additional","affiliation":[{"name":"Department of Metabolic Health Research, The Netherlands Organisation for Applied Scientific Research (TNO), 2333 CK Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4996-943X","authenticated-orcid":false,"given":"Martine","family":"Morrison","sequence":"additional","affiliation":[{"name":"Department of Metabolic Health Research, The Netherlands Organisation for Applied Scientific Research (TNO), 2333 CK Leiden, The Netherlands"},{"name":"Human and Animal Physiology, Wageningen University, 6708 WD Wageningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0248-4008","authenticated-orcid":false,"given":"Martien","family":"Caspers","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Systems Biology, The Netherlands Organization for Applied Scientific Research (TNO), 3704 HE Zeist, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wim","family":"van Duyvenvoorde","sequence":"additional","affiliation":[{"name":"Department of Metabolic Health Research, The Netherlands Organisation for Applied Scientific Research (TNO), 2333 CK Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marieke","family":"Heijnk","sequence":"additional","affiliation":[{"name":"Center for Proteomics and Metabolomics, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1684-1894","authenticated-orcid":false,"given":"Martin","family":"Giera","sequence":"additional","affiliation":[{"name":"Center for Proteomics and Metabolomics, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Bobeldijk-Pastorova","sequence":"additional","affiliation":[{"name":"Department of Metabolic Health Research, The Netherlands Organisation for Applied Scientific Research (TNO), 2333 CK Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9720-7491","authenticated-orcid":false,"given":"Jaap","family":"Keijer","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Systems Biology, The Netherlands Organization for Applied Scientific Research (TNO), 3704 HE Zeist, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Storsve","sequence":"additional","affiliation":[{"name":"Aker BioMarine Antarctic AS, Oksen\u00f8yveien 10, NO-1366 Lysaker, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4542-1290","authenticated-orcid":false,"given":"Petter-Arnt","family":"Hals","sequence":"additional","affiliation":[{"name":"Aker BioMarine Antarctic AS, Oksen\u00f8yveien 10, NO-1366 Lysaker, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1350-0149","authenticated-orcid":false,"given":"Robert","family":"Kleemann","sequence":"additional","affiliation":[{"name":"Department of Metabolic Health Research, The Netherlands Organisation for Applied Scientific Research (TNO), 2333 CK Leiden, The Netherlands"},{"name":"Department of Vascular Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1038\/nature21363","article-title":"Inflammation, metaflammation and immunometabolic disorders","volume":"542","author":"Hotamisligil","year":"2017","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Longo, M., Zatterale, F., Naderi, J., Parrillo, L., Formisano, P., Raciti, G.A., Beguinot, F., and Miele, C. 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