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Background: High intakes of trans-fatty acids (TFAs), especially industrially produced TFAs, can lead to unfavorable lipid and lipoprotein concentrations and an increased risk of cardiovascular disease. It is unknown how this relation might change in a population after significant reductions in TFA intake.Objective: This study, which used a new analytical method for measuring plasma TFA concentrations, clarified the association between plasma TFA and serum lipid and lipoprotein concentrations before and after the US FDA enacted TFA food-labeling regulations in 2006.Methods: Data were selected from the NHANES of 1999-2000 and 2009-2010. Findings on 1383 and 2155 adults, respectively, aged ≥20 y, were evaluated. Multivariable linear regressions were used to examine the associations between plasma TFA concentration and lipid and lipoprotein concentrations. The outcome measures were serum concentrations of total cholesterol (TC), LDL cholesterol, HDL cholesterol, and triglycerides and the ratio of TC to HDL cholesterol.Results: The median plasma TFA concentration decreased from 80.6 μmol/L in 1999-2000 to 37.0 μmol/L in 2009-2010. Plasma TFA concentration continued to be associated with serum lipid and lipoprotein concentrations after significant reductions in TFA intake in the population. For example, by comparing the lowest with the highest quintiles of TFA concentration in 1999-2000, adjusted mean (95% CI) LDL-cholesterol concentrations increased from 118 mg/dL (112, 123 mg/dL) to 135 mg/dL (130, 141 mg/dL) (P-trend < 0.001). The corresponding values for 2009-2010 were 102 mg/dL (97.4, 107 mg/dL) and 129 mg/dL (125, 133 mg/dL) for LDL cholesterol (P-trend < 0.001). Differences between the highest and lowest quintiles were consistent across age groups, sexes, races/ethnicities, and other covariates.Conclusions: Despite a 54% reduction in plasma TFA concentrations in US adults from 1999-2000 to 2009-2010, concentrations remained significantly associated with serum lipid and lipoprotein concentrations. There does not appear to be a threshold under which the association between plasma TFA concentration and lipid profiles might become undetectable. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of cancer deaths worldwide. In the United States, only one in six lung cancer patients survives five years after diagnosis. These statistics may improve if new therapeutic targets are identified. We previously reported that an enzyme of fatty acid metabolism, very long-chain acyl-CoA synthetase 3 (ACSVL3), is overexpressed in malignant glioma, and that depleting glioblastoma cells of ACSVL3 diminishes their malignant properties. To determine whether ACSVL3 expression was also increased in lung cancer, we studied tumor histologic sections and lung cancer cell lines. Immunohistochemical analysis of normal human lung showed moderate ACSVL3 expression only in bronchial epithelial cells. In contrast, all of 69 different lung tumors tested, including adeno-, squamous cell, large cell, and small cell carcinomas, had robustly elevated ACSVL3 levels. Western blot analysis of lung cancer cell lines derived from these tumor types also had significantly increased ACSVL3 protein compared to normal bronchial epithelial cells. Decreasing the growth rate of lung cancer cell lines did not change ACSVL3 expression. However, knocking down ACSVL3 expression by RNA interference reduced cell growth rates in culture by 65–76%, and the ability of tumor cells to form colonies in soft agar suspension by 65–80%. We also conducted studies to gain a better understanding of the biochemical properties of human ACSVL3. ACSVL3 mRNA was detected in many human tissues, but the expression pattern differed somewhat from that of the mouse. The enzyme activated long- and very long-chain saturated fatty acid substrates, as well as long-chain mono- and polyunsaturated fatty acids to their respective coenzyme A derivatives. Endogenous human ACSVL3 protein was found in a punctate subcellular compartment that partially colocalized with mitochondria as determined by immunofluorescence microscopy and subcellular fractionation. From these studies, we conclude that ACSVL3 is a promising new therapeutic target in lung cancer. [ABSTRACT FROM AUTHOR]

The lipemic response to a high-fat meal is greater in men than in women. However, sex-related differences in the metabolic fate of ingested fat are not well understood. The purpose of this study was to measure the recovery of ingested fat in plasma fractions of chylomicrons (CHYLO), VLDL, and plasma fatty acids, as well as in expired breath (i.e., oxidation) in men and women. Nonobese subjects (n = 10; 5 men, 5 women) consumed 0.7 g fat/kg body weight containing 7 mg/kg of [1,1,1-13C]-trioleate the morning after an overnight fast. Plasma total triglyceride (TG) concentration and 13C recovery in the CHYLO, VLDL, and plasma fatty acid fractions, as well as expired breath samples, were measured over the 11-h period after the meal. Plasma total TG excursion was greater (P < 0.05) in men than in women during the 11-h period after the meal. Similarly, the recovery of the ingested tracer-labeled fat in the CHYLO fraction was greater in men than in women (main effect for sex; P < 0.05). Recovery of ingested tracer-labeled fat in VLDL, the plasma fatty acid fraction, and expired breath did not differ in men and women. Therefore, the elevated postprandial lipemia found in men compared with women was due to a prolonged availability of the lipid in chylomicrons, but was not related to differences in oxidation rates or incorporation of the ingested lipid into VLDL by the liver. [ABSTRACT FROM AUTHOR]