Revisiting intervertebral disc degeneration: lipid metabolism disorders as overlooked contributors to complex pathology.

With the global population aging, intervertebral disc degeneration (IDD), an aging-related disease, has been confirmed to be an important cause of low back pain (LBP). LBP can affect people of all ages and has now become one of the leading noncommunicable diseases, resulting in reduced life expectancy and functional disability in patients. Previous studies have mostly focused on the effects of factors such as mechanical load and genetics on intervertebral disc degeneration. With the deepening of research, the focus has gradually shifted to metabolic disorders, among which lipid metabolism plays a non-negligible role. Lipid metabolism is involved in the construction of cell structure and microenvironment, which is crucial for maintaining normal physiological functions. Abnormal levels of free fatty acids, triglycerides, and cholesterol are widely recognized as risk factors for intervertebral disc degeneration. Lipid metabolism disorders participate in the pathological process of intervertebral disc degeneration through the following pathways: affecting the release of pro-inflammatory cytokines, activating oxidative stress, inducing excessive autophagy, and triggering endoplasmic reticulum stress. Meanwhile, these four pathways can synergistically exacerbate intervertebral disc degeneration. This paper reviews studies on the association between lipid metabolism disorders and intervertebral disc degeneration, focusing on the underlying pathological mechanisms, so as to provide new insights for further exploring the treatment and intervention strategies of intervertebral disc degeneration, and emphasizes the significance of lipid metabolism in maintaining intervertebral disc health.