Electroacupuncture regulates lipid metabolism through PPARγ-associated LXRα signaling: from nuclear receptor signaling to cardiovascular protection

Hyperlipidemia is an independent risk factor for atherosclerotic cardiovascular disease, and a substantial proportion of patients remain inadequately controlled on statin therapy because single-target interventions cannot fully reverse the systemic inflammation and tissue injury driven by dysregulated lipid metabolism. Electroacupuncture (EA), a modern refinement of traditional acupuncture,has been reported to lower serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol in clinical trials, yet the molecular basis of these effects has not been systematically synthesized. Here, we review the evidence that EA regulates lipid homeostasis through the peroxisome proliferator-activated receptor γ (PPAR γ )/liver X receptor α (LXR α ) axis. We first outline the structure and function of these nuclear receptors and their transcriptional crosstalk, and then examine how EA modulates their expression, activity, and co-regulators. We next trace the upstream signal transduction from somatic afferent activation through the neuro–endocrine–immune network, and the downstream effector programs, including cholesterol efflux, fatty-acid oxidation, macrophage M2 polarization, and organ-specific cardiovascular protection. Pharmacological antagonism, PPAR γ knockdown, and MerTK deficiency provide causal evidence that the PPAR γ -associated efferocytic program contributes to the lipid-lowering and efferocytic effects of EA, whereas the involvement of LXR α is supported primarily by its coordinated expression with PPAR γ and downstream cholesterol-efflux signaling. We conclude by discussing the heterogeneity of EA parameters, the animal-to-human translational gap, and the limitations of causal inference in the current literature, and outline future directions, including optogenetic dissection of acupuncture neural circuits and PPAR γ /LXR α -guided standardization of EA protocols.