{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T02:13:27Z","timestamp":1774318407335,"version":"3.50.1"},"reference-count":58,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T00:00:00Z","timestamp":1702425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2019s Horizon 2020 research and innovation programme","award":["739582"],"award-info":[{"award-number":["739582"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation programme","award":["664620"],"award-info":[{"award-number":["664620"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation programme","award":["BG05M2OP001-1.003-001-C01"],"award-info":[{"award-number":["BG05M2OP001-1.003-001-C01"]}]},{"name":"European Regional Development Fund","award":["739582"],"award-info":[{"award-number":["739582"]}]},{"name":"European Regional Development Fund","award":["664620"],"award-info":[{"award-number":["664620"]}]},{"name":"European Regional Development Fund","award":["BG05M2OP001-1.003-001-C01"],"award-info":[{"award-number":["BG05M2OP001-1.003-001-C01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Obesity prevalence is becoming a serious global health and economic issue and is a major risk factor for concomitant diseases that worsen the quality and duration of life. Therefore, the urgency of the development of novel therapies is of a particular importance. A previous study of ours revealed that the natural pterocarpan, maackiain (MACK), significantly inhibits adipogenic differentiation in human adipocytes through a peroxisome proliferator-activated receptor gamma (PPAR\u03b3)-dependent mechanism. Considering the observed anti-adipogenic potential of MACK, we aimed to further elucidate the molecular mechanisms that drive its biological activity in a Caenorhabditis elegans obesity model. Therefore, in the current study, the anti-obesogenic effect of MACK (25, 50, and 100 \u03bcM) was compared to orlistat (ORST, 12 \u03bcM) as a reference drug. Additionally, the hybrid combination between the ORST (12 \u03bcM) and MACK (100 \u03bcM) was assessed for suspected synergistic interaction. Mechanistically, the observed anti-obesogenic effect of MACK was mediated through the upregulation of the key metabolic regulators, namely, the nuclear hormone receptor 49 (nhr-49) that is a functional homologue of the mammalian PPARs and the AMP-activated protein kinase (aak-2\/AMPK) in C. elegans. Collectively, our investigation indicates that MACK has the potential to limit lipid accumulation and control obesity that deserves future developments.<\/jats:p>","DOI":"10.3390\/ijms242417442","type":"journal-article","created":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T08:55:16Z","timestamp":1702457716000},"page":"17442","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Maackiain Mimics Caloric Restriction through aak-2-Mediated Lipid Reduction in Caenorhabditis elegans"],"prefix":"10.3390","volume":"24","author":[{"given":"Saveta G.","family":"Mladenova","sequence":"first","affiliation":[{"name":"Independent Researcher, 1000 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monika N.","family":"Todorova","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolomics, Institute of Microbiology, Bulgarian Academy of Sciences, 139 Ruski Blvd., 4000 Plovdiv, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3852-8658","authenticated-orcid":false,"given":"Martina S.","family":"Savova","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolomics, Institute of Microbiology, Bulgarian Academy of Sciences, 139 Ruski Blvd., 4000 Plovdiv, Bulgaria"},{"name":"Department of Plant Cell Biotechnology, Center of Plant Systems Biology and Biotechnology, 4000 Plovdiv, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5248-6135","authenticated-orcid":false,"given":"Milen I.","family":"Georgiev","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolomics, Institute of Microbiology, Bulgarian Academy of Sciences, 139 Ruski Blvd., 4000 Plovdiv, Bulgaria"},{"name":"Department of Plant Cell Biotechnology, Center of Plant Systems Biology and Biotechnology, 4000 Plovdiv, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1690-1490","authenticated-orcid":false,"given":"Liliya V.","family":"Mihaylova","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolomics, Institute of Microbiology, Bulgarian Academy of Sciences, 139 Ruski Blvd., 4000 Plovdiv, Bulgaria"},{"name":"Department of Plant Cell Biotechnology, Center of Plant Systems Biology and Biotechnology, 4000 Plovdiv, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/s41392-022-01149-x","article-title":"Signaling pathways in obesity: Mechanisms and therapeutic interventions","volume":"7","author":"Wen","year":"2022","journal-title":"Signal Transduct. 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