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The reinforcing hedonic properties of high-fat foods, including olfactory cues, activate reward centers in the brain, motivating eating behavior. Thus, there is a growing interest in the understanding of the genetic changes that occur in the brain that are associated with obesity and eating behavior. This growing interest has paralleled advances in genomic methods that enable transcriptomic-wide analyses. Here, we examined the transcriptomic-level differences in the olfactory bulb and striatum, regions of the brain associated with olfaction and hedonic food-seeking, respectively, in high-fat-diet (HFD)-fed obese mice. To isolate the dietary effects from obesity, we also examined transcriptomic changes in normal-chow-fed and limited-HFD-fed groups, with the latter being pair-fed with an HFD isocaloric to the consumption of the normal-chow-fed mice. Using RNA sequencing, we identified 274 differentially expressed genes (DEGs) in the striatum and 11 in the olfactory bulb of ad libitum HFD-fed mice compared to the chow-fed group, and thirty-eight DEGs in the striatum between the ad libitum HFD and limited-HFD-fed groups. The DEGs in both tissues were associated with inflammation and immune-related pathways, including oxidative stress and immune function, and with mitochondrial dysfunction and reward pathways in the striatum. These results shed light on potential obesity-associated genes in these regions of the brain.<\/jats:p>","DOI":"10.3390\/ijms25179330","type":"journal-article","created":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T07:52:08Z","timestamp":1724831528000},"page":"9330","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Diet-Induced Obesity Induces Transcriptomic Changes in Neuroimmunometabolic-Related Genes in the Striatum and Olfactory Bulb"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5726-7529","authenticated-orcid":false,"given":"Rosario B.","family":"Jaime-Lara","sequence":"first","affiliation":[{"name":"National Institute of Alcohol Abuse and Alcoholism, Bethesda, MD 20892, USA"},{"name":"National Institute of Nursing Research, Bethesda, MD 20892, USA"},{"name":"School of Nursing, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9670-0543","authenticated-orcid":false,"given":"Claudia","family":"Colina-Prisco","sequence":"additional","affiliation":[{"name":"National Institute of Alcohol Abuse and Alcoholism, Bethesda, MD 20892, USA"},{"name":"National Institute of Nursing Research, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"De Jesus Vega","sequence":"additional","affiliation":[{"name":"National Institute of Alcohol Abuse and Alcoholism, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Williams","sequence":"additional","affiliation":[{"name":"National Institute of Mental Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ted","family":"Usdin","sequence":"additional","affiliation":[{"name":"National Institute of Mental Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bridget","family":"Matikainen-Ankney","sequence":"additional","affiliation":[{"name":"Department of Psychology, Rutgers University, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alayna","family":"Kinkead","sequence":"additional","affiliation":[{"name":"National Institute of Nursing Research, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4596-0657","authenticated-orcid":false,"given":"Brianna","family":"Brooks","sequence":"additional","affiliation":[{"name":"National Institute of Nursing Research, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yupeng","family":"Wang","sequence":"additional","affiliation":[{"name":"National Institute of Nursing Research, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0550-334X","authenticated-orcid":false,"given":"Alexis T.","family":"Franks","sequence":"additional","affiliation":[{"name":"National Institute of Nursing Research, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexxai","family":"Kravitz","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Washington University in St. Louis, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1198-9622","authenticated-orcid":false,"given":"Paule V.","family":"Joseph","sequence":"additional","affiliation":[{"name":"National Institute of Alcohol Abuse and Alcoholism, Bethesda, MD 20892, USA"},{"name":"National Institute of Nursing Research, Bethesda, MD 20892, USA"},{"name":"National Smell and Taste Center, National Institute on Deafness and Other Communication Disorders, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"21","DOI":"10.3810\/pgm.2009.11.2074","article-title":"The medical risks of obesity","volume":"121","year":"2009","journal-title":"Postgrad. 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