Abstract
The effect of weight loss from long-term, mild-calorie diets (MCD) on plasma metabolites is unknown. This study was to examine whether MCD-induced weight reduction caused changes in the extended plasma metabolites. Overweight and obese subjects aged 40-59 years consumed a MCD (approximately 100 kcal/day deficit, n=47) or a weight-maintenance diet (control, n=47) in a randomized, controlled design with a three-year clinical intervention period and plasma samples were analyzed by using UPLC-LTQ-Orbitrap mass spectrometry. The three-year MCD intervention resulted in weight loss (-8.87%) and significant decreases in HOMA-IR and TG. The three-year follow-up of the MCD group showed reductions in the following 13 metabolites: L-leucine; L-phenylalanine; 9 lysoPCs; PC (18:0/20:4); and SM (d18:0/16:1). The three-year MCD group follow-up identified increases in palmitic amide, oleamide, and PC (18:2/18:2). Considering the age-related alterations in the identified metabolites, the MCD group showed a greater decrease in L-leucine, L-phenylalanine, and SM (d18:0/16:1) compared with those of the control group. Overall, the change (Δ) in BMI positively correlated with the ΔTG, ΔHOMA-IR, ΔL-leucine, and ΔSM (d18:0/16:1). The ΔHOMA-IR positively correlated with ΔTG, ΔL-leucine, ΔL-phenylalanine, and ΔSM (d18:0/16:1). The weight loss resulting from three-year mild-caloric restriction lessens the age-related increase in SM and reduces L-leucine and L-phenylalanine in overweight and obese subjects. These changes were coupled with improved insulin resistance (ClinicalTrials.gov: NCT02081898).
Highlights
The effect of weight loss from long-term, mild-calorie diets (MCD) on plasma metabolites is unknown
We expected to investigate what metabolic changes occurred during weight loss when it was induced by long-term MCD in overweight and obese subjects, and we considered that the observed changes could be possible biomarkers for predicting the future risk of a disease arising under overweight and obese conditions, facilitating the design of early interventions to prevent disease progression
There were no significant differences between the control group and the MCD group in the following baseline characteristics: gender (25 males and 22 females in both groups), age, body weight, body mass index (BMI), waist circumference, blood pressure (BP), total, LDL, and HDL-cholesterol, free fatty acid (FFA), glucose, insulin, homeostasis-model assessment (HOMA)-insulin resistance (IR) index, and Lipoprotein-associated phospholipase A2 (Lp-PLA2) activity (Table 1)
Summary
The effect of weight loss from long-term, mild-calorie diets (MCD) on plasma metabolites is unknown. The weight loss resulting from three-year mildcaloric restriction lessens the age-related increase in SM and reduces L-leucine and L-phenylalanine in overweight and obese subjects. These changes were coupled with improved insulin resistance (ClinicalTrials.gov: NCT02081898). We expected to investigate what metabolic changes occurred during weight loss when it was induced by long-term MCD in overweight and obese subjects, and we considered that the observed changes could be possible biomarkers for predicting the future risk of a disease arising under overweight and obese conditions, facilitating the design of early interventions to prevent disease progression. The objective of this study was to examine whether the reduction induced by MCD (an approximately 100 kcal/day deficit) changed the extended plasma metabolite profile in middle aged overweight and obese subjects during a three-year intervention study
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