👤 Paula V Gaete

Childhood obesity is associated with alterations in lipoprotein metabolism and increased oxidative stress, assessed by lipid peroxidation products, reactive oxygen species (ROS) and nitric oxide (NO) levels, oxidized/reduced glutathione (GSH/GSSG) ratio, and the activities of superoxide dismutase (SOD) and catalase. High-density lipoproteins (HDL) play an antioxidant role, conditioned by cholesteryl ester transfer protein (CETP), paraoxonase (PON) 1, lecithin:cholesterol acyltransferase (LCAT), lipoprotein-associated phospholipase A This study aims to evaluate HDL antioxidant capacity in children and adolescents with obesity and the status of its conditioning factors. Thirty children and adolescents, 15 with obesity and 15 normal-weight controls were studied in a cross-sectional observational study. Lipid profile and high-sensitivity C-reactive protein were assessed using standardized methods. Lipid peroxidation products, ROS, NO, GSH and GSSG levels, and catalase, SOD, CETP, LCAT, PON 1 (PON and arylesterase [ARE]) and Lp-PLA Children with obesity showed lower HDL cholesterol and apo A-I levels (P < .01), reduced CETP (P < .05), ARE (Lp-PLA Children and adolescents with obesity exhibited reduced HDL antioxidant activity, alterations in its conditioning factors, intrinsic oxidative modification of HDL particles, and increased oxidative stress. These alterations may affect long-term cardiovascular risk in children and adolescents with obesity. Show less

The genetic substrate of severe hypertriglyceridemia (sHTG) in Latin America is insufficiently understood. To identify genetic variants in genes related to triglyceride (TG) metabolism among adults with sHTG from Colombia. In individuals with plasma TG ≥ 880 mg/dL at least once in their lifetime, we amplified and sequenced all exons and intron/exon boundaries of the genes LPL, APOC2, APOA5, GPIHBP1 and LMF1. For each variant we ascertained its location, zygosity, allelic frequency and pathogenicity classification according to American College of Medical Genetics (ACMG) criteria. The study included 166 participants (62% male, mean age 50 years), peak TG levels ranged between 894 and 11,000 mg/dL. We identified 92 variants: 19 in LPL, 7 in APOC2, 11 in GPIHBP1, 38 in LMF1, and 17 in APOA5. Eighteen of these variants had not been reported. We identified a new pathogenic variant in LMF1 (c.41C>A; p.Ser14*), a new likely pathogenic variant in LMF1 (c.1527 C > T; p.Pro509=, also expressed as c.1447C>T; p.Gln483*), and a known pathogenic variant in LMF1 (c.779G>A; p.Trp260*). Four participants were heterozygous for variant c.953A>G; p.Asn318Ser in LPL, a known risk factor for hypertriglyceridemia. Participants with variants of unknown significance (VUS) in LMF1 had significantly higher peak TG than those with VUS in other genes. Peak TG were 4317 mg/dL in participants with a history of pancreatitis, and 1769 mg/dL in those without it (p = 0.001). Our study identified variants associated with sHTG among Latinos, and showed that genetic variation in LMF1 may be frequently associated with sHTG in this population. Show less

Abdominal obesity is an important cardiovascular disease risk factor. Plasma fatty acids display a complex network of both pro and antiatherogenic effects. High density lipoproteins (HDL) carry out the antiatherogenic pathway called reverse cholesterol transport (RCT), which involves cellular cholesterol efflux (CCE), and lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) activities. Our aim was to characterize RCT and its relation to fatty acids present in plasma in pediatric abdominal obesity. Seventeen children and adolescents with abdominal obesity and 17 healthy controls were studied. Anthropometric parameters were registered. Glucose, insulin, lipid levels, CCE employing THP-1 cells, LCAT and CETP activities, plus fatty acids in apo B-depleted plasma were measured. The obese group showed a more atherogenic lipid profile, plus lower CCE (Mean±Standard Deviation) (6 ± 2 vs. 7 ± 2%; P < 0.05) and LCAT activity (11 ± 3 vs. 15 ±5 umol/dL.h; P < 0.05). With respect to fatty acids, the obese group showed higher myristic (1.1 ± 0.3 vs. 0.7 ± 0.3; P < 0.01) and palmitic acids (21.5 ± 2.8 vs. 19.6 ± 1.9; P < 0.05) in addition to lower linoleic acid (26.4 ± 3.3 vs. 29.9 ± 2.6; P < 0.01). Arachidonic acid correlated with CCE (r = 0.37; P < 0.05), myristic acid with LCAT (r = -0.37; P < 0.05), palmitioleic acid with CCE (r = -0.35; P < 0.05), linoleic acid with CCE (r = 0.37; P < 0.05), lauric acid with LCAT (r = 0.49; P < 0.05), myristic acid with LCAT (r = -0.37; P < 0.05) ecoisatrienoic acid with CCE (r = 0.40; P < 0.05) and lignoseric acid with LCAT (r = -0.5; P < 0.01). Children and adolescents with abdominal obesity presented impaired RCT, which was associated with modifications in proinflammatory fatty acids, such as palmitoleic and myristic, thus contributing to increased cardiovascular disease risk. Show less