The impact of low carbohydrate diet on the plasma proteomic profile of individuals with obesity.

INTRODUCTION: Obesity is a major public health concern worldwide and contributes to multiple metabolic disorders. Low carbohydrate diets (LCDs) have been proposed as an effective strategy for weight management and metabolic improvement; however, the mechanisms underlying LCD-induced molecular changes in individuals with obesity remain incompletely understood. This study aimed to assess the impact of a three-month LCD on the proteomic profile of adults with obesity. METHODS: Thirty adults (18-50 years) with obesity (BMI ≥ 30 kg/m2) followed an LCD (60-110 g/day) for 3 months. Anthropometric and laboratory measurements were obtained, and blood samples were collected at baseline and endpoint. Changes in the plasma proteomic profile were evaluated using an untargeted label-free quantitative proteomics approach (LC-MS/MS), complemented by bioinformatics and pathway network analyses. Anthropometric and biochemical data were analyzed using paired-sample t-tests and Wilcoxon signed-rank tests in IBM SPSS®. RESULTS: Overall, the LCD was associated with significant reductions in body weight, BMI, waist and hip circumferences, fat mass and percentage, GGT, triglycerides, and HbA1c (paired t-test, p < 0.001). Participants were stratified by total weight loss percentage into responders (≥5%; n = 15) and non-responders (<5%; n = 15). Label-free proteomics identified 90 significantly dysregulated proteins in responders (53 upregulated, 37 downregulated) and 183 in non-responders (111 upregulated, 72 downregulated) between baseline and endpoint. Significantly dysregulated proteins in the responder group included beta-enolase (ENO3) and CREG1 (both upregulated), and tenascin (downregulated). In the non-responder group, insulin-like growth factor-binding protein 7, acyl-CoA-binding protein, and talin-1 were significantly downregulated. Pathway network analysis in responders was centered around dysregulation of TNF, IL6, IFNG, APP, DEGS1, and ENO3 and was related to cell-mediated immune response, cell-to-cell signaling and interaction, and cellular movement. In non-responders, the top network was centered around PGAM1, PDIA3, PHGDH, and EGFR and was associated with cardiovascular disease, dermatological diseases and conditions, and organismal injury and abnormalities. CONCLUSION: A three-month LCD significantly improved anthropometric and metabolic parameters in adults with obesity and was associated with marked changes in the plasma proteome. Distinct proteomic signatures between responders and non-responders highlight inter-individual variability in biological response, supporting the potential of plasma proteomics for biomarker discovery and precision nutrition in obesity management.