{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T08:05:34Z","timestamp":1784016334218,"version":"3.55.0"},"reference-count":32,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["JDC2024\u2010053319\u2010I"],"award-info":[{"award-number":["JDC2024\u2010053319\u2010I"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["FPU18\/00666"],"award-info":[{"award-number":["FPU18\/00666"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["EST22\/00052"],"award-info":[{"award-number":["EST22\/00052"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sertoli cells (SCs) provide essential metabolic support for spermatogenesis, including lactate production for developing germ cells. While insulin's role in SC glucose metabolism is well\u2010established, its regulation of fatty acid (FA) uptake and oxidation\u2014critical for germ cell support and residual body clearance\u2014remains unknown. Insulin deficiency in diabetes mellitus (DM) impairs male fertility through mechanisms that may involve disrupted SC metabolism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To determine whether insulin regulates FA uptake and oxidation in SCs and to elucidate mechanistic links between insulin deficiency and impaired spermatogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      The TM4 mouse SC line was cultured under defined in vitro conditions in the presence of insulin (10 \u00b5g\/mL) versus under insulin\u2010deprived conditions for 18 h. FA metabolism was assessed using RT\u2010qPCR (FAT\/CD36, ACADL, and CPT1A), Western blotting,\n                      <jats:sup>1<\/jats:sup>\n                      H\u2010NMR spectroscopy, functional FA uptake assay, Oil Red O staining, JC\u20101 mitochondrial assessment, and Seahorse real\u2010time metabolic analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Insulin deprivation significantly reduced glucose consumption, glutamine consumption, and lactate production. FAT\/CD36 expression and FA uptake capacity decreased markedly, with reduced intracellular lipid droplet accumulation. Conversely, FA oxidation enzyme expression (CPT1A, ACADL) remained unchanged, as did mitochondrial membrane potential and oxygen consumption rates with\/without etomoxir.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion and Conclusion<\/jats:title>\n                    <jats:p>In the TM4 mouse SC line under defined in vitro conditions, insulin selectively regulates FA uptake while maintaining no control over downstream FA oxidation. This dissociation reveals that insulin modulates FA entry for storage and\/or biosynthesis, while FA oxidation operates constitutively. Impaired FA uptake under insulin deficiency may compromise SC support for spermatogenesis, providing a mechanistic link to male infertility in DM that requires confirmation in primary SCs and in vivo diabetic models.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/andr.70316","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T07:40:41Z","timestamp":1784014841000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Insulin Regulates CD36\u2010Dependent Fatty Acid Uptake but Not Mitochondrial Oxidation in Sertoli Cells"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0685-7534","authenticated-orcid":false,"given":"Marc","family":"Llavanera","sequence":"first","affiliation":[{"name":"Department of Animal Genetics Centre For Research in Agricultural Genomics (CRAG) CSIC\u2010IRTA\u2010UAB\u2010UB Campus De La Universitat Aut\u00f2noma De Barcelona  Bellaterra Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana D.","family":"Martins","sequence":"additional","affiliation":[{"name":"LAQV\u2010REQUIMTE and Department of Chemistry University of Aveiro  Aveiro Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlota","family":"Santos","sequence":"additional","affiliation":[{"name":"LAQV\u2010REQUIMTE and Department of Chemistry University of Aveiro  Aveiro Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel L.","family":"Bernardino","sequence":"additional","affiliation":[{"name":"UMIB \u2010 Unit for Multidisciplinary Research in Biomedicine ICBAS \u2010 School of Medicine and Biomedical Sciences University of Porto  Porto Portugal"},{"name":"Laboratory for Integrative and Translational Research in Population Health (ITR) University of Porto  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7635-783X","authenticated-orcid":false,"given":"Marco G.","family":"Alves","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine (iBiMED) Department of Medical Sciences University of Aveiro  Aveiro Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1461-8875","authenticated-orcid":false,"given":"Pedro F.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"LAQV\u2010REQUIMTE and Department of Chemistry University of Aveiro  Aveiro Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2021.06.016"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2014\u20101101"},{"key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/978-3-319-19791-3_5","volume-title":"Sertoli Cell Metabolism and Spermatogenesis","author":"Oliveira P. 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