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Neuroinflammation, modulated by glial cells, is a crucial event during the neurodegenerative process; consequently, there is an urgency to find new therapeutic products with anti-glioinflammatory properties. Five new furanocembranolides (1\u22125), along with leptolide, were isolated from two different extracts of Leptogorgia sp., and compound 6 was obtained from chemical transformation of leptolide. Their structures were determined based on spectroscopic evidence. These seven furanocembranolides were screened in vitro by measuring their ability to modulate interleukin-1\u03b2 (IL-1\u03b2) production by microglial BV2 cells after LPS (lipopolysaccharide) stimulation. Leptolide and compounds 3, 4 and 6 exhibited clear anti-inflammatory effects on microglial cells, while compound 2 presented a pro-inflammatory outcome. The in vitro results prompted us to assess anti-glioinflammatory effects of leptolide in vivo in a high-fat diet-induced obese mouse model. Interestingly, leptolide treatment ameliorated both microgliosis and astrogliosis in this animal model. Taken together, our results reveal a promising direct biological effect of furanocembranolides on microglial cells as bioactive anti-inflammatory molecules. Among them, leptolide provides us a feasible therapeutic approach to treat neuroinflammation concomitant with metabolic impairment.<\/jats:p>","DOI":"10.3390\/md18080378","type":"journal-article","created":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T10:14:06Z","timestamp":1595499246000},"page":"378","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Modulation of Glial Responses by Furanocembranolides: Leptolide Diminishes Microglial Inflammation in Vitro and Ameliorates Gliosis In Vivo in a Mouse Model of Obesity and Insulin Resistance"],"prefix":"10.3390","volume":"18","author":[{"given":"Miriam","family":"Corraliza-G\u00f3mez","sequence":"first","affiliation":[{"name":"Instituto de Biolog\u00eda y Gen\u00e9tica Molecular, Universidad de Valladolid-CSIC, 47003 Valladolid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amalia B.","family":"Gallardo","sequence":"additional","affiliation":[{"name":"Instituto de Productos Naturales y Agrobiolog\u00eda (IPNA-CSIC), Avenida Astrof\u00edsico F. S\u00e1nchez, 3, 38206 La Laguna, Tenerife, Spain"},{"name":"Departamento de Ciencias y Recursos Naturales, Facultad de Ciencias, Universidad de Magallanes, Avenida Bulnes 01855, Punta Arenas, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8886-7519","authenticated-orcid":false,"given":"Ana R.","family":"D\u00edaz-Marrero","sequence":"additional","affiliation":[{"name":"Instituto de Productos Naturales y Agrobiolog\u00eda (IPNA-CSIC), Avenida Astrof\u00edsico F. S\u00e1nchez, 3, 38206 La Laguna, Tenerife, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 M.","family":"de la Rosa","sequence":"additional","affiliation":[{"name":"Instituto de Productos Naturales y Agrobiolog\u00eda (IPNA-CSIC), Avenida Astrof\u00edsico F. 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