Background: Clinical studies have demonstrated that higher protein intake based on caloric restriction (CR) alleviates metabolic abnormalities. However, no study has examined the effects of plasma protein profiles on caloric restriction with protein supplementation (CRPS) in metabolic syndrome (MetS). Therefore, using a proteomic perspective, this pilot study investigated whether CRPS ameliorated metabolic abnormalities associated with MetS in middle-aged women. Methods: Plasma samples of middle-aged women with MetS in CR (n
= 7) and CRPS (n
= 6) groups for a 12-week intervention were obtained and their protein profiles were analysed. Briefly, blood samples from qualified participants were drawn before and after the dietary treatment. Anthropometric, clinical, and biochemical variables were measured and correlated with plasma proteomics. Results: In results, we found that body mass index, total body fat, and fasting blood glucose decreased significantly after the interventions but were not different between the CR and CRPS groups. After liquid chromatography–tandem mass spectrometry analysis, the relative plasma levels of alpha-2-macroglobulin (A2M), C4b-binding protein alpha chain (C4BPA), complement C1r subcomponent-like protein (C1RL), complement component C6 (C6), complement component C8 gamma chain (C8G), and vitamin K-dependent protein S (PROS) were significantly different between the CRPS and CR groups. These proteins are involved in inflammation, the immune system, and coagulation responses. Moreover, blood low-density lipoprotein cholesterol levels were significantly and positively correlated with C6 plasma levels in both groups. Conclusions: These findings suggest that CRPS improves inflammatory responses in middle-aged women with MetS. Specific plasma protein expression (i.e., A2M, C4BPA, C1RL, C6, C8G, and PROS) associated with the complement system was highly correlated with fasting blood glucose (FBG), blood lipids (BLs), and body fat.
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