# The Vicious Cycle of Obesity and Low Back Pain: A Comprehensive Review
## 4 Spinal Changes Related to Obesity
### Intervertebral Disc  
Within the IVD, the NP and AF are particularly vulnerable to the metabolic stress associated with obesity. Obesity triggers chronic low-grade inflammation marked by elevated pro-inflammatory cytokines, which promote ECM degradation through increased matrix-degrading enzymes and cellular stress, while apoptosis and senescence reduce ECM-producing cells [33]. Here, the primary endocrine and paracrine mediators of this obesity-induced metabolic dysfunction are likely adipokines [91], whose role is described in detail below. The connection between obesity and IDD has been well documented in preclinical animal models. Experimental mouse models subjected to high-fat diets (HFD), which result in elevated systemic lipid levels, exhibit altered IVD metabolism characterized by increased apoptosis and ECM degradation [67; 68; 92]. Similar degenerative changes are observed in other cartilage tissues, such as knee joints [67]. These ECM changes are accompanied by a loss of disc height, reduced hydration, and a significant increase in inflammatory factors such as TNF-\(\alpha\), Monocyte Chemoattractant Protein (MCP)-1, vascular endothelial growth factor (VEGF), and IL-1B [67; 68]. Since obesity is often accompanied by diabetes, it is noteworthy that hyperglycemia can directly impair IVD integrity in murine models. While hyperglycemia can increase the glycosaminoglycan and collagen content of the disc, it also promotes the accumulation of advanced glycation end-products (AGEs), leading to disorganized AF lamellae and reduced mechanical strength and elasticity [70]. In a mouse model, excessive dietary AGE intake resulted in increased collagen cross-linking and AF damage, ultimately leading to higher IVD compressive stiffness, torque range, and failure torque, particularly in female animals [71]. Additionally, glucose may dose-dependently upregulate a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 and -5 through activation of the CREB-binding protein (CBP)-PPARy coactivator 1\(\alpha\) (PGC1\(\alpha\))-Runx2 complex, further contributing to IVD ECM breakdown [69]. \begin{table}
\begin{tabular}{c c c c} \hline
**Tissue** & **Structural Changes** & **Functional Changes** & **Ref** \\ \hline NP & Loss of proteoglycans & Reduced ability to resist compression & \\  & Decreased water content & Loss of mechanical shock absorption & [33; 67; 68; 69] \\  & AGE accumulation & Loss in spinal height and stability & \\  & Fibrotic changes & & \\  & Disruption of lamellar structure & Decreased tensile strength and & \\  & AGE accumulation & increased stiffness & \\  & Fibrotic changes & Loss of structural integrity and & [70; 71] \\  & Microtears & containment of NP & \\  & Thinning and calcification & Reduced nutrient and waste & \\  & CEP & Impaired permeability & \\  & Microfractures & Loss of NP environment containment & [64; 72; 73; 74; 75; 76; 77; 78; 79] \\  & Osteoarthritic changes & Development of focal defects & \\  & Joint effusion & Reduced spinal stability & \\  & Increased fatty infiltration & Compression of neighbouring tissues & [80; 81; 82] \\  & PSMs & Reduced muscle fibre size & \\  & Muscle atrophy & & \\  & Excessive fat accumulation & Increased risk of spinal stenosis and & \\  & Compression of adjacent nervous & cauda equina syndrome & [86; 87; 88; 89; 90] \\  & structures & Compression-related pain & \\ \hline  & Abbreviations: AF (annulus fibrosis); AGE (advanced glycation end-product); CEP (cartilaginous endplate); NP (nucleus pulposus); PSM (parasignal muscle). & \\ \end{tabular}
\end{table} 
Table 1: Overview of obesity-related changes associated with IDD and LBP. Like the NP and AF, the CEP is also vulnerable to obesity-induced mechanical, metabolic, and inflammatory stressors, which heighten the risk of microfractures and structural damage.