BackgroundOmega (n)-3 polyunsaturated fatty acids (PUFA) are converted to bioactive lipid components that are important mediators in metabolic and physiological pathways; however, which bioactive compounds are metabolically active, and their mechanisms of action are still not clear. We investigated using lipidomic techniques, the effects of diets high in n-3 PUFA on the fatty acid composition of various bioactive lipids in plasma and liver.Methodology and Principal FindingsFemale C57BL/6 mice were fed semi-purified diets (20% w/w fat) containing varying amounts of n-3 PUFA before mating, during gestation and lactation, and until weaning. Male offspring were continued on their mothers’ diets for 16 weeks. Hepatic and plasma lipids were extracted in the presence of non-naturally occurring internal standards, and tandem electrospray ionization mass spectrometry methods were used to measure the fatty acyl compositions. There was no significant difference in total concentrations of phospholipids in both groups. However, there was a significantly higher concentration of eicosapentaenoic acid containing phosphatidylcholine (PC), lysophosphatidylcholine (LPC), and cholesteryl esters (CE) (p < 0.01) in the high n-3 PUFA group compared to the low n-3 PUFA group in both liver and plasma. Plasma and liver from the high n-3 PUFA group also had a higher concentration of free n-3 PUFA (p < 0.05). There were no significant differences in plasma concentrations of different fatty acyl species of phosphatidylethanolamine, triglycerides, sphingomyelin and ceramides.Conclusions/SignificanceOur findings reveal for the first time that a diet high in n-3 PUFA caused enrichment of n-3 PUFA in PC, LPC, CE and free fatty acids in the plasma and liver of C57BL/6 mice. PC, LPC, and unesterified free n-3 PUFA are important bioactive lipids, thus altering their fatty acyl composition will have important metabolic and physiological roles.

BackgroundOmega-3 polyunsaturated fatty acids (n-3 PUFA) have been shown to alleviate the symptoms of metabolic disorders, such as heart disease, diabetes, obesity and insulin resistance. Several putative mechanisms by which n-3 PUFA elicit beneficial health effects have been proposed; however, there is still a shortage of knowledge on the proteins and pathways that are regulated by n-3 PUFA.MethodsUsing two dimensional polyacrylamide gel electrophoresis (2D-PAGE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, we investigated the effects of diets high or low in n-3 PUFA on hepatic proteomic profile of C57BL/6 mice.ResultsThe findings show for the first time that high dietary n-3 PUFA reduced the expression of regucalcin, adenosine kinase and aldehyde dehydrogenase. On the other hand, diets high in n-3 PUFA increased the expression of apolipoprotein A-I, S-adenosylmethionine synthase, fructose-1, 6-bisphosphatase, ketohexokinase, malate dehydrogenase, GTP-specific succinyl CoA synthase, ornithine aminotransferase and protein disulfide isomerase-A3.ConclusionsOur findings revealed for the first time that n-3 PUFA causes alterations in several novel functional proteins involved in regulating lipid, carbohydrate, one-carbon, citric acid cycle and protein metabolism, suggesting integrated regulation of metabolic pathways. These novel proteins are potential targets to develop therapeutic strategies against metabolic disorders.

Our data suggest that the decrease in progesterone levels observed in HIV-infected pregnant women exposed to PI-based cART is caused, at least in part, by an increase in placental expression of 20α-HSD, which may be due to lower prolactin levels observed in these women.

Introducion With the increasing number of children exposed to HIV or antiretroviral therapy in utero, there are concerns that this population may have worse neurodevelopmental outcomes compared to those who are unexposed. The objective of this study was to systematically review the clinical and preclinical literature on the effects of in utero exposure to HIV and/or antiretroviral therapy ( ART ) on neurodevelopment. Methods We systematically searched OVID Medline, Psyc INFO and Embase, as well as the Cochrane Collaborative Database, Google Scholar and bibliographies of pertinent articles. Titles, abstracts, and full texts were assessed independently by two reviewers. Data from included studies were extracted. Results are summarized qualitatively. Results The search yielded 3027 unique titles. Of the 255 critically reviewed full‐text articles, 25 met inclusion criteria for the systematic review. Five articles studied human subjects and looked at brain structure and function. The remaining 20 articles were preclinical studies that mostly focused on behavioural assessments in animal models. The few clinical studies had mixed results. Some clinical studies found no difference in white matter while others noted higher fractional anisotropy and lower mean diffusivity in the brains of HIV ‐exposed uninfected children compared to HIV ‐unexposed uninfected children, correlating with abnormal neurobehavioral scores. Preclinical studies focused primarily on neurobehavioral changes resulting from monotherapy with either zidovudine or lamivudine. Various developmental and behavioural changes were noted in preclinical studies with ART exposure, including decreased grooming, decreased attention, memory deficits and fewer behaviours associated with appropriate social interaction. Conclusions While the existing literature suggests that there may be some neurobehavioral differences associated with HIV and ART exposure, limited data are available to substantially support these claims. More research is needed comparing neurobiological factors between HIV ‐exposed uninfected and HIV ‐unexposed uninfected children and using exposures consistent with current clinical care.