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Impaired metabolism has also been reported in the offspring of obese fathers. However, whether brain function can also be affected by paternal obesity has barely been examined. This study aimed to characterize the learning deficits resulting from paternal obesity versus those induced by maternal obesity and to identify the underlying mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Founder control and obese female and male Wistar rats were mated to constitute three first\u2010generation (F1) experimental groups: control mother\/control father, obese mother\/control father, and obese father\/control mother. All F1 animals were weaned onto standard chow and underwent a learning test at 4 months of age, after which several markers of glutamate\u2010mediated synaptic plasticity together with the expression of miRNAs targeting glutamate receptors and the concentration of kynurenic and quinolinic acids were quantified in the hippocampus and frontal cortex.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Maternal obesity induced a severe learning deficit by impairing memory encoding and memory consolidation. The offspring of obese fathers also showed reduced memory encoding but not impaired long\u2010term memory formation. Memory deficits in offspring of obese fathers and obese mothers were associated with a down\u2010regulation of genes encoding NMDA glutamate receptors subunits and several learning\u2010related genes along with impaired expression of miR\u2010296 and miR\u2010146b and increased concentration of kynurenic acid.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Paternal and maternal obesity impair offspring's learning abilities by affecting different processes of memory formation. These cognitive deficits are associated with epigenetic and neurochemical alterations leading to impaired glutamate\u2010mediated synaptic plasticity.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.14090","type":"journal-article","created":{"date-parts":[[2024,1,17]],"date-time":"2024-01-17T10:39:49Z","timestamp":1705487989000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Adult rats sired by obese fathers present learning deficits associated with epigenetic and neurochemical alterations linked to impaired brain glutamatergic signaling"],"prefix":"10.1111","volume":"240","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2389-1796","authenticated-orcid":false,"given":"Carla Elena","family":"Mezo\u2010Gonz\u00e1lez","sequence":"first","affiliation":[{"name":"UMR Physiologie des Adaptations Nutritionnelles INRAE \u2013 Nantes Universit\u00e9  Nantes 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