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Obesity is a risk factor for IVD degeneration and promotes the release of pro\u2010inflammatory cytokines from adipocytes, leading to inflammation and triggering catabolic degenerative pathways. Western diets high in omega\u20106 fatty acids (n\u20106 FAs) exacerbate inflammation and obesity, increasing the risk for musculoskeletal diseases. Conversely, omega\u20103 (n\u20103) FA enriched diets may mitigate these adverse effects. The nonmammalian\n                      <jats:italic>fat\u20101<\/jats:italic>\n                      gene converts n\u20106 to n\u20103 FAs, thereby reducing n\u20106:n\u20103 ratios and systemic inflammation. This study aims to elucidate the role of n\u20106:n\u20103 FA ratios in IVD degeneration by comparing wildtype (WT) and\n                      <jats:italic>fat\u20101<\/jats:italic>\n                      transgenic mice fed n\u20106 enriched HFD (n\u20106 HFD).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Male and female WT and\n                      <jats:italic>fat\u20101<\/jats:italic>\n                      transgenic mice were fed control or n\u20106\u2010HFD. Body composition (weight, adiposity) and disc height index (DHI) were assessed at 16\u2009weeks of age using microCT imaging. Chronic effects were evaluated at 60\u2009weeks of age via serum cytokines (inflammatory panel), bone parameters (microCT), DHI, and histological grading of H&amp;E staining.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At 16 weeks, HFD increased adiposity, while\n                      <jats:italic>fat\u20101<\/jats:italic>\n                      mice exhibited reduced weight gain. In\u00a0vivo microCT revealed lower DHI in HFD\u2010fed animals but higher DHI in\n                      <jats:italic>fat\u20101<\/jats:italic>\n                      groups, with sex and lumbar level differences. At 60\u2009weeks, inflammatory cytokines (IL\u20106, IL\u201017A) were elevated in the serum of WT HFD mice compared to\n                      <jats:italic>fat\u20101<\/jats:italic>\n                      HFD mice. Histopathological staining revealed increased fibrosis, cell loss, and matrix disorganization in the IVDs of HFD\u2010fed WT mice. However, IVDs of\n                      <jats:italic>fat\u20101<\/jats:italic>\n                      mice were protected from the degenerative effects of HFD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Lowering the n\u20106:n\u20103 FA ratio via endogenous\n                      <jats:italic>fat\u20101<\/jats:italic>\n                      activity modulates systemic inflammatory profiles in a sex\u2010dependent manner and protects against obesity\u2010driven IVD degeneration. These findings highlight the potential of dietary interventions or\n                      <jats:italic>fat\u20101<\/jats:italic>\n                      gene therapy for treating obesity\u2010associated IVD pathology.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jsp2.70206","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T09:09:41Z","timestamp":1785143381000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transgenic Conversion of Omega\u20106 to Omega\u20103 Fatty Acids via\n                    <i>fat\u20101<\/i>\n                    Reduces Obesity\u2010Related Intervertebral Disc Degeneration"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8807-2348","authenticated-orcid":false,"given":"Shirley N.","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery Washington 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