Background/Objectives:Inter-individual variability in weight loss during obesity treatment is complex and poorly understood. Here we use whole body and tissue approaches to investigate fuel oxidation characteristics in skeletal muscle fibers, cells and distinct circulating protein biomarkers before and after a high fat meal (HFM) challenge in those who lost the most (obese diet-sensitive; ODS) vs the least (obese diet-resistant; ODR) amount of weight in a highly controlled weight management program.Subjects/Methods:In 20 weight stable-matched ODS and ODR women who previously completed a standardized clinical weight loss program, we analyzed whole-body energetics and metabolic parameters in vastus lateralis biopsies and plasma samples that were obtained in the fasting state and 6 h after a defined HFM, equivalent to 35% of total daily energy requirements.Results:At baseline (fasting) and post-HFM, muscle fatty acid oxidation and maximal oxidative phosphorylation were significantly greater in ODS vs ODR, as was reactive oxygen species emission. Plasma proteomics of 1130 proteins pre and 1, 2, 5 and 6 h after the HFM demonstrated distinct group and interaction differences. Group differences identified S-formyl glutathione hydratase, heat shock 70 kDA protein 1A/B (HSP72), and eukaryotic translation initiation factor 5 (eIF5) to be higher in ODS vs ODR. Group-time differences included aryl hydrocarbon interacting protein (AIP), peptidylpropyl isomerase D (PPID) and tyrosine protein-kinase Fgr, which increased in ODR vs ODS over time. HSP72 levels correlated with muscle oxidation and citrate synthase activity. These proteins circulate in exosomes; exosomes isolated from ODS plasma increased resting, leak and maximal respiration rates in C2C12 myotubes by 58%, 21% and 51%, respectively, vs those isolated from ODR plasma.Conclusions:Findings demonstrate distinct muscle metabolism and plasma proteomics in fasting and post-HFM states corresponding in diet-sensitive vs diet-resistant obese women.

Objective: The aim of the present study was to investigate the combined impact of visceral adipose tissue (VAT) and secretory group IIA phospholipase A 2 (sPLA 2 -IIA) concentrations on the atherogenicity of low-density lipoprotein (LDL) particles among men. Subjects: Analyses were conducted in 74 mid-obese healthy men (age: (mean7s.d.) 37.9711.7 years). Methods: Plasma levels of sPLA 2 -IIA were measured with a commercial ELISA and VAT levels were assessed by computed tomography. Distinct subpopulations of LDL particles were characterized from whole plasma using nondenaturating 2-16% gradient gel electrophoresis. Results: Data indicated that plasma sPLA 2 -IIA levels were approximately 29% (P ¼ 0.007) higher among men characterized by a higher accumulation of VAT (4142 vs p142 cm 2 ). Men having high plasma sPLA 2 -IIA levels (X127.2 ng/dl, the median value), were characterized by higher levels of plasma cholesterol (C) and apolipoprotein (apo) B, LDL-C, LDL-apoB, oxidized LDL (OxLDL) and by smaller LDL particles compared to men with sPLA 2 -IIAo127.2 ng/dl. Multiple regression analyses showed that plasma triglycerides and sPLA 2 -IIA levels explained 22.7 and 11.8% of the variance in LDL peak particle size, respectively. Levels of VAT and of sPLA 2 -IIA were the strongest correlates of OxLDL levels explaining, respectively, 15.0 and 5.5% of their variability. Conclusion: Both VAT and sPLA 2 -IIA levels modulate the atherogenecity of LDL by accounting for the reduction in their size and their susceptibility to oxidation.