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Mol. Life Sci."],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Obesity-associated dysfunctional intestinal permeability contributes to systemic chronic inflammation leading to the development of metabolic diseases. The inflammasomes constitute essential components in the regulation of intestinal homeostasis. We aimed to determine the impact of the inflammasomes in the regulation of gut barrier dysfunction and metabolic inflammation in the context of obesity and type 2 diabetes (T2D).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Blood samples obtained from 80 volunteers (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200920 normal weight,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200921 OB without T2D,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200939 OB with T2D) and a subgroup of jejunum samples were used in a case\u2013control study. Circulating levels of intestinal damage markers and expression levels of inflammasomes as well as their main effectors (IL-1\u03b2 and IL-18) and key inflammation-related genes were analyzed. The impact of inflammation-related factors, different metabolites and\n                      <jats:italic>Akkermansia muciniphila<\/jats:italic>\n                      in the regulation of inflammasomes and intestinal integrity genes was evaluated. The effect of blocking\n                      <jats:italic>NLRP6<\/jats:italic>\n                      by using siRNA in inflammation was also studied.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Increased circulating levels (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.01) of the intestinal damage markers endotoxin, LBP, and zonulin in patients with obesity decreased (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05) after weight loss. Patients with obesity and T2D exhibited decreased (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05) jejunum gene expression levels of\n                      <jats:italic>NLRP6<\/jats:italic>\n                      and its main effector\n                      <jats:italic>IL18<\/jats:italic>\n                      together with increased (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05) mRNA levels of inflammatory markers. We further showed that while NLRP6 was primarily localized in goblet cells, NLRP3 was localized in the intestinal epithelial cells. Additionally, decreased (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05) mRNA levels of\n                      <jats:italic>Nlrp1<\/jats:italic>\n                      ,\n                      <jats:italic>Nlrp3<\/jats:italic>\n                      and\n                      <jats:italic>Nlrp6<\/jats:italic>\n                      in the small intestinal tract obtained from rats with diet-induced obesity were found.\n                      <jats:italic>NLRP6<\/jats:italic>\n                      expression was regulated by taurine, parthenolide and\n                      <jats:italic>A. muciniphila<\/jats:italic>\n                      in the human enterocyte cell line CCL-241. Finally, a significant decrease (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.01) in the expression and release of\n                      <jats:italic>MUC2<\/jats:italic>\n                      after the knockdown of\n                      <jats:italic>NLRP6<\/jats:italic>\n                      was observed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The increased levels of intestinal damage markers together with the downregulation of\n                      <jats:italic>NLRP6<\/jats:italic>\n                      and\n                      <jats:italic>IL18<\/jats:italic>\n                      in the jejunum in obesity-associated T2D suggest a defective inflammasome sensing, driving to an impaired epithelial intestinal barrier that may regulate the progression of multiple obesity-associated comorbidities.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00018-024-05124-3","type":"journal-article","created":{"date-parts":[[2024,2,5]],"date-time":"2024-02-05T08:02:21Z","timestamp":1707120141000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Decreased expression of the NLRP6 inflammasome is associated with increased intestinal permeability and inflammation in obesity with type 2 diabetes"],"prefix":"10.1007","volume":"81","author":[{"given":"Gema","family":"Fr\u00fchbeck","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"G\u00f3mez-Ambrosi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Ram\u00edrez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Becerril","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amaia","family":"Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amaia","family":"Mentxaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00edctor","family":"Valent\u00ed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Moncada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Reina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Baixauli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos","family":"Casado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilo","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Escalada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7513-7509","authenticated-orcid":false,"given":"Victoria","family":"Catal\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,5]]},"reference":[{"key":"5124_CR1","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1007\/s00125-003-1053-4","volume":"46","author":"G Fr\u00fchbeck","year":"2003","unstructured":"Fr\u00fchbeck G, G\u00f3mez-Ambrosi J (2003) Control of body weight: a physiologic and transgenic perspective. 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