Proteomics and metabolomics analysis of Mongolian acupuncture therapy for type 2 diabetes mellitus with atherosclerosis

Mongolian acupuncture therapy, a traditional modality involving stimulation of specific acupoints, has shown notable benefits in managing diabetes mellitus (DM) and its complications. However, its effects and molecular mechanisms in type 2 DM (T2DM) complicated with atherosclerosis remain unclear. This study aimed to evaluate the therapeutic efficacy and elucidate the molecular mechanisms of Mongolian acupuncture in a rat model of T2DM with atherosclerosis. A T2DM with atherosclerosis rat model was established using high-fat/high-sugar diet feeding, streptozotocin injection, and vitamin D3 administration. Rats were treated with Mongolian acupuncture for 28 days. Serum biochemical parameters and inflammatory markers were assessed. Histopathological changes in the carotid artery were examined by hematoxylin and eosin (H&E) staining. Proteomic and metabolomic analyses were performed to identify differentially expressed proteins (DEPs) and metabolites (DEMs), and key protein changes were validated by Western blot. Mongolian acupuncture significantly improved inflammatory cytokine levels, renal function markers, lipid profiles, and carotid artery histopathology compared with untreated model rats. Proteomics identified 625 DEPs enriched mainly in fatty acid metabolism and energy metabolism pathways. Metabolomics revealed 184 DEMs, with enrichment in linoleic acid, sphingolipid, and amino acid metabolism. Integrated analysis suggested that the therapeutic effects were largely mediated by regulation of fatty acid metabolism, supported by increased expression of HADH, ACADL, ACSF3, and CPT1B, and elevated palmitoleic acid levels. Mongolian acupuncture alleviates vascular and metabolic dysfunction in T2DM with atherosclerosis, potentially through modulation of fatty acid metabolism and energy homeostasis. These findings provide mechanistic insights and experimental evidence supporting the potential clinical application of Mongolian acupuncture for T2DM-associated macrovascular complications.