Transgenic Conversion of Omega‐6 to Omega‐3 Fatty Acids viaReduces Obesity‐Related Intervertebral Disc Degeneration
Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine
ABSTRACT Introduction Low back pain is a leading cause of disability, largely due to intervertebral disc (IVD) degeneration. Obesity is a risk factor for IVD degeneration and promotes the release of pro‐inflammatory cytokines from adipocytes, leading to inflammation and triggering catabolic degenerative pathways. Western diets high in omega‐6 fatty acids (n‐6 FAs) exacerbate inflammation and obesity, increasing the risk for musculoskeletal diseases. Conversely, omega‐3 (n‐3) FA enriched diets may mitigate these adverse effects. The nonmammaliangene converts n‐6 to n‐3 FAs, thereby reducing n‐6:n‐3 ratios and systemic inflammation. This study aims to elucidate the role of n‐6:n‐3 FA ratios in IVD degeneration by comparing wildtype (WT) andtransgenic mice fed n‐6 enriched HFD (n‐6 HFD). jsp270206-sec-0001 Methods Male and female WT andtransgenic mice were fed control or n‐6‐HFD. Body composition (weight, adiposity) and disc height index (DHI) were assessed at 16 weeks of age using microCT imaging. Chronic effects were evaluated at 60 weeks of age via serum cytokines (inflammatory panel), bone parameters (microCT), DHI, and histological grading of H&E staining. jsp270206-sec-0002 Results At 16 weeks, HFD increased adiposity, whilemice exhibited reduced weight gain. In vivo microCT revealed lower DHI in HFD‐fed animals but higher DHI ingroups, with sex and lumbar level differences. At 60 weeks, inflammatory cytokines (IL‐6, IL‐17A) were elevated in the serum of WT HFD mice compar
Abstract
ABSTRACT Introduction Low back pain is a leading cause of disability, largely due to intervertebral disc (IVD) degeneration. Obesity is a risk factor for IVD degeneration and promotes the release of pro‐inflammatory cytokines from adipocytes, leading to inflammation and triggering catabolic degenerative pathways. Western diets high in omega‐6 fatty acids (n‐6 FAs) exacerbate inflammation and obesity, increasing the risk for musculoskeletal diseases. Conversely, omega‐3 (n‐3) FA enriched diets may mitigate these adverse effects. The nonmammaliangene converts n‐6 to n‐3 FAs, thereby reducing n‐6:n‐3 ratios and systemic inflammation. This study aims to elucidate the role of n‐6:n‐3 FA ratios in IVD degeneration by comparing wildtype (WT) andtransgenic mice fed n‐6 enriched HFD (n‐6 HFD). jsp270206-sec-0001 Methods Male and female WT andtransgenic mice were fed control or n‐6‐HFD. Body composition (weight, adiposity) and disc height index (DHI) were assessed at 16 weeks of age using microCT imaging. Chronic effects were evaluated at 60 weeks of age via serum cytokines (inflammatory panel), bone parameters (microCT), DHI, and histological grading of H&E staining. jsp270206-sec-0002 Results At 16 weeks, HFD increased adiposity, whilemice exhibited reduced weight gain. In vivo microCT revealed lower DHI in HFD‐fed animals but higher DHI ingroups, with sex and lumbar level differences. At 60 weeks, inflammatory cytokines (IL‐6, IL‐17A) were elevated in the serum of WT HFD mice compared toHFD mice. Histopathological staining revealed increased fibrosis, cell loss, and matrix disorganization in the IVDs of HFD‐fed WT mice. However, IVDs ofmice were protected from the degenerative effects of HFD. jsp270206-sec-0003 Conclusions Lowering the n‐6:n‐3 FA ratio via endogenousactivity modulates systemic inflammatory profiles in a sex‐dependent manner and protects against obesity‐driven IVD degeneration. These findings highlight the potential of dietary interventions orgene therapy for treating obesity‐associated IVD pathology. jsp270206-sec-0004 We investigated whether transgenic conversion of omega‐6 to omega‐3 fatty acids mitigates obesity‐associated intervertebral disc () degeneration. Usingmice on a high‐fat diet, we observed that endogenous omega‐3 production prevented diet‐induced disc pathology, metabolic dysfunction, and reduced systemic inflammation, indicating a protective role for omega‐3 fatty acids in obesity‐relatedpathology. graphical