SUMMARY Genome-wide association studies have identified GALNT2 as a candidate gene in lipid metabolism, but it is not known how the encoded enzyme ppGal-NAc-T2, which contributes to the initiation of mucin-type O-linked glycosylation, mediates this effect. In two probands with elevated plasma high-density lipoprotein cholesterol and reduced triglycerides, we identified a mutation in GALNT2. It is shown that carriers have improved postprandial triglyceride clearance, which is likely attributable to attenuated glycosylation of apolipoprotein (apo) C-III, as observed in their plasma. This protein inhibits lipoprotein lipase (LPL), which hydrolyses plasma triglycerides. We show that an apoC-III-based peptide is a substrate for ppGalNAc-T2 while its glycosylation by the mutant enzyme is impaired. In addition, neuraminidase treatment of apoC-III which removes the sialic acids from its glycan chain decreases its potential to inhibit LPL. Combined, these data suggest that ppGalNAc-T2 can affect lipid metabolism through apoC-III glycosylation, thereby establishing GALNT2 as a lipid-modifying gene.

BackgroundAdditive manufacturing (AM) is a rapidly expanding new technology involving challenges to occupational health. Here, metal exposure in an AM facility with large-scale metallic component production was investigated during two consecutive years with preventive actions in between.MethodsGravimetric analyzes measured airborne particle concentrations, and filters were analyzed for metal content. In addition, concentrations of airborne particles <300 nm were investigated. Particles from recycled powder were characterized. Biomonitoring of urine and dermal contamination among AM operators, office personnel, and welders was performed.ResultsTotal and inhalable dust levels were almost all below occupational exposure limits, but inductively coupled plasma mass spectrometry showed that AM operators had a significant increase in cobalt exposure compared with welders. Airborne particle concentrations (<300 nm) showed transient peaks in the AM facility but were lower than those of the welding facility. Particle characterization of recycled powder showed fragmentation and condensates enriched in volatile metals. Biomonitoring showed a nonsignificant increase in the level of metals in urine in AM operators. Dermal cobalt and a trend for increasing urine metals during Workweek Year 1, but not in Year 2, indicated reduced exposure after preventive actions.ConclusionGravimetric analyses showed low total and inhalable dust exposure in AM operators. However, transient emission of smaller particles constitutes exposure risks. Preventive actions implemented by the company reduced the workers' metal exposure despite unchanged emissions of particles, indicating a need for careful design and regulation of the AM environments. It also emphasizes the need for relevant exposure markers and biomonitoring of health risks.

The heterogeneity of atherosclerotic tissue has limited comprehension in proteomic and metabolomic analyses. To elucidate the functional implications, and differences between genders, of atherosclerotic lesion formation we investigated protein profiles from different regions of human carotid atherosclerotic arteries; internal control, fatty streak, plaque shoulder, plaque centre, and fibrous cap. Proteomic analysis was performed using 2-DE with MALDI-TOF, with validation using nLC-MS/MS. Protein mapping of 2-DE identified 52 unique proteins, including 15 previously unmapped proteins, of which 41 proteins were confirmed by nLC-MS/MS analysis. Expression levels of 18 proteins were significantly altered in plaque regions compared to the internal control region. Nine proteins showed site-specific alterations, irrespective of gender, with clear associations to extracellular matrix remodelling. Five proteins display gender-specific alterations with 2-DE, with two alterations validated by nLC-MS/MS. Gender differences in ferritin light chain and transthyretin were validated using both techniques. Validation of immunohistochemistry confirmed significantly higher levels of ferritin in plaques from male patients. Proteomic analysis of different plaque regions has reduced the effects of plaque heterogeneity, and significant differences in protein expression are determined in specific regions and between genders. These proteomes have functional implications in plaque progression and are of importance in understanding gender differences in atherosclerosis.

BackgroundThe aim of the study was to find a simple intravenous glucose tolerance test (IVGTT) that can be used to estimate insulin sensitivity.MethodsIn 20 healthy volunteers aged between 18 and 51 years (mean, 28) comparisons were made between kinetic parameters derived from a 12-sample, 75-min IVGTT and the Mbw (glucose uptake) obtained during a hyperinsulinemic euglycemic glucose clamp. Plasma glucose was used to calculate the volume of distribution (Vd) and the clearance (CL) of the injected glucose bolus. The plasma insulin response was quantified by the area under the curve (AUCins). Uptake of glucose during the clamp was corrected for body weight (Mbw).ResultsThere was a 7-fold variation in Mbw. Algorithms based on the slope of the glucose-elimination curve (CL/Vd) in combination with AUCins obtained during the IVGTT showed statistically significant correlations with Mbw, the linearity being r2 = 0.63-0.83. The best algorithms were associated with a 25-75th prediction error ranging from -10% to +10%. Sampling could be shortened to 30-40 min without loss of linearity or precision.ConclusionSimple measures of glucose and insulin kinetics during an IVGTT can predict between 2/3 and 4/5 of the insulin sensitivity.