{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:05:35Z","timestamp":1791925535520,"version":"4.3.4"},"reference-count":107,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,9,22]],"date-time":"2020-09-22T00:00:00Z","timestamp":1600732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["PG\/17\/43\/33041"],"award-info":[{"award-number":["PG\/17\/43\/33041"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and objectives: Overnutrition leads to a metabolic and inflammatory response that includes the activation of Complement. Properdin is the only amplifier of complement activation and increases the provision of complement activation products. Its absence has previously been shown to lead to increased obesity in mice on a high fat diet. The aim of this study was to determine ways in which properdin contributes to a less pronounced obese phenotype. Materials and Methods: Wild type (WT) and properdin deficient mice (KO) were fed a high-fat diet (HFD) for up to 12 weeks. Results: There was a significant increase in liver triglyceride content in the KO HFD group compared to WT on HFD. WT developed steatosis. KO had an additional inflammatory component (steatohepatitis). Analysis of AKT signalling by phosphorylation array supported a decrease in insulin sensitivity which was greater for KO than WT in liver and kidney. There was a significant decrease of C5L2 in the fat membranes of the KO HFD group compared to the WT HFD group. Circulating microparticles in KO HFD group showed lower presence of C5L2. Expression of the fatty acid transporter CD36 in adipose tissue was increased in KO on HFD and was also significantly increased in plasma of KO HFD mice compared to WT on HFD. CD36 was elevated on microparticles from KO on HFD. Ultrastructural changes consistent with obesity-associated glomerulopathy were observed for both HFD fed genotypes, but tubular strain was greater in KO. Conclusion: Our work demonstrates that complement properdin is a dominant factor in limiting the severity of obesity-associated conditions that impact on liver and kidney. The two receptors, C5L2 and CD36, are downstream of the activity exerted by properdin.<\/jats:p>","DOI":"10.3390\/medicina56090484","type":"journal-article","created":{"date-parts":[[2020,9,22]],"date-time":"2020-09-22T09:40:56Z","timestamp":1600767656000},"page":"484","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Complement Properdin Regulates the Metabolo-Inflammatory Response to a High Fat Diet"],"prefix":"10.3390","volume":"56","author":[{"given":"R\u1f79is\u00edn C.","family":"Thomas","sequence":"first","affiliation":[{"name":"Department of Respiratory Sciences, University of Leicester, Leicester LE1 9HN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3039-4920","authenticated-orcid":false,"given":"Ramiar","family":"Kheder","sequence":"additional","affiliation":[{"name":"Department of Respiratory Sciences, University of Leicester, Leicester LE1 9HN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasanain","family":"Alaridhee","sequence":"additional","affiliation":[{"name":"Department of Respiratory Sciences, University of Leicester, Leicester LE1 9HN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6242-6977","authenticated-orcid":false,"given":"Naomi","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Respiratory Sciences, University of Leicester, Leicester LE1 9HN, UK"},{"name":"Faculty of Health and Life Sciences, De Montfort University, Leicester LE1 9BH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0125-4868","authenticated-orcid":false,"given":"Cordula M.","family":"Stover","sequence":"additional","affiliation":[{"name":"Department of Respiratory Sciences, University of Leicester, Leicester LE1 9HN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.smim.2013.04.003","article-title":"The role of the complement system in metabolic organs and metabolic diseases","volume":"25","author":"Phieler","year":"2013","journal-title":"Semin. 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