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Objectives

While chronic obesity is associated with alterations in circulating glycerolipids, sphingolipids and plasmalogens, the effects of short-term overfeeding in humans are unclear.

Design and Methods

Healthy individuals (n = 40) were overfed by 1,250 kcal day−1 for 28 days. Insulin sensitivity (hyperinsulinemic-euglycemic clamp), abdominal fat distribution and serum lipidomics (mass spectrometry) were assessed.

Results

Overfeeding increased liver fat, insulin resistance, serum C-reactive protein and urinary F2-isoprostanes. HDL increased (11% ± 2%, P < 0.001) while LDL, triglycerides and nonesterified fatty acids were unchanged. Three hundred and thirty three serum lipids were detected, of which 13% increased and 20% decreased with overfeeding. Total diacylglycerol and lysoalkylphosphatidylcholine (LPC(O)) concentrations decreased (P < 0.01), while total ceramide, Cer22:0 and Cer24:0 increased (P ≤ 0.01). The most notable increases were observed in the HDL-associated phosphatidylethanolamine-based plasmalogens and their precursors alkylhosphatidylethanolamine (18 ± 5% and 38 ± 8% respectively, P ≤ 0.01).

Conclusions

Overfeeding led to weight gain and changes in the serum lipid profile. Increases in ceramides were noted, which left unchecked may promote systemic insulin resistance. Uniform increases were observed in plasmalogens and their precursors. Because plasmalogens are powerful antioxidants, this may be an appropriate response against increased oxidative stress generated by over-nutrition. The metabolic consequences of changes in concentrations of many circulating lipid species with overfeeding require further study. Copyright © 2013 The Obesity Society