Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries

Correction: Volume: 9, Article Number: 3493 DOI: 10.1038/s41467-018-05975-y Published: AUG 23 2018Lipoprotein(a), Lp(a), is a modified low- density lipoprotein particle that contains apolipoprotein( a), encoded by LPA, and is a highly heritable, causal risk factor for cardiovascular diseases that varies in concentrations across ancestries. Here, we use deep-coverage whole genome sequencing in 8392 individuals of European and African ancestry to discover and interpret both single-nucleotide variants and copy number (CN) variation associated with Lp(a). We observe that genetic determinants between Europeans and Africans have several unique determinants. The common variant rs12740374 associated with Lp(a) cholesterol is an eQTL for SORT1 and independent of LDL cholesterol. Observed associations of aggregates of rare non-coding variants are largely explained by LPA structural variation, namely the LPA kringle IV 2 (KIV2)-CN. Finally, we find that LPA risk genotypes confer greater relative risk for incident atherosclerotic cardiovascular diseases compared to directly measured Lp(a), and are significantly associated with measures of subclinical atherosclerosis in African Americans.Peer reviewe

Histochemical Studies on the Nervous and Humoral Regulation of Lipids and Carbohydrate Metabolism

The purpose of the present study is to reveal the precise mechanism of nervous and humoral regulations of lipid and carbohydrate metabolisms in the adipose tissues. Histochemical and biochemical observations were made on the innervated and denervated interscapular brown adipose tissues and partly on the liver and adrenal cortex of male mice during starvation with or without carbohydrate introduction with special consideration to the changes of the lipid and glycogen contents and to the activities of several important enzymes as well as to pH values in the tissues. In a state of absolute starvation, the animals died in a few days showing a gradual discharge of stored lipids from the innervated brown adipose tissues, while in the denervated tissues the stored lipids increased gradually even in a state of slight or moderate starvation as well as in the cases of normally fed animals. The increase of lipids continued before the stage of severe starvation and the stored lipids being rapidly discharged became nil at the terminal stage of life. Introduction of glucose into starved animals caused also a more marked deposition of glycogen in the denervated than in the innervated tissues in proportion to the degree of starvation, although it did not cause the deposition in both tissues at the terminal stage of life. These facts represent that the nervous regulation is essential for the mobilization of lipids and carbohydrates from this tissue. Adrenalectomy also caused the death of animals within a few days with a gradual decrease of depot lipids. In this case denervation likewise caused a marked depositon of lipids in the brown adipose tissues, showing a sudden escape of lipids at the end of life. Experiments on transplanted adipose tissues taken from the animals at the terminal stage of starvation, proved that the tissue cells retain the ability to deposit lipids until the end of life. Chemical estimation elucidated that the serum glucose and lipids fall markedly at the terminal stage of life. The innervated tissues showed increased activities of succinic dehydrogenase, alkaline phosphatase, ATPase and lipase during starvation with a gradual discharge of lipids. Glucose injection increased the degree of the activities of all these enzymes, though in the terminal stage of starvation the ATPase activity declined again. The activity of total cholinesterase declined slightly in severe starvation. The pH value fell gradually with the progress of starvation. On the other hand, in the denervated tissues the activity of succinic dehydrogenase fell with an increased deposition of lipids, though in the final stage of starvation the activity rose with the discharge of lipids; while the activities of phosphatase, ATPase and lipase rose during starvation and total, unspecific and specific cholinesterase activities declined slightly. The pH value in the denervated tissues rose slightly during mild starvation and fell markedly in severe starvation. Observations proved that the activities Df these enzymes and pH, which are under the control of the autonomic nervous system, have close relationships to the deposition and the discharge of lipids and glycogen from the adipose tissues, and that the rapid discharge of lipids from the denervated tissue at the terminal stage of life is an expression of the onesided progress of oxidative process which may mean a complete loss of regulation of metabolism.</p

Editorial: Membrane lipids in T cell functions

Plasma membrane lipids play essential roles in regulating T cell signaling, differentiation, and effector functions. The major lipid species in the plasma membrane are glycerophospholipids, sphingolipids, and sterol lipids. TCR and costimulatory molecules lead to profound changes in the composition, distribution, and dynamic of plasma membrane lipids. For instance, cholesterol, sphingomyelin, and saturated phosphocholine are enriched at the contact zone between T cells and antigen-presenting cells during peptide/MHC complexes recognition, where they constitute a platform of lipid domains essential for optimal T cell signaling. Glycerophospholipid provide docking sites for binding pivotal signaling proteins as well as for their conformation, portioning, and mobility. Finally, plasma membrane lipids also act as second messengers with important immune-regulatory functions. This Research Topic contains seven articles that review the current understanding of the mechanisms and molecules involved in the metabolism and function of membrane lipids and how differences in their content may affect T cell functional properties

New perspective in fisheries product development: importance of seaweeds as biomass resources

Brown seaweeds have an important role to preserve coastal ecosystems. Brown seaweeds are also major class for aquacultured seaweeds. They contain valuable nutrients and bioactive components and some of them have not been found in terrestrial plants. Especially, much attention has been paid to brown seaweed lipids because of their high functionality. Several brown seaweeds show high total lipids (TL) contents, ranging from 10-20 wt% per dry weight. The lipids are rich in functional 18:4n-3, 20:5n-3 and 20:4n-6. Brown seaweed TL also contains fucoxanthin as a key functional compound. Brown seaweed lipids show anti-obesity and anti-diabetic effects, which are mainly due to the up-regulatory effect of fucoxanthin on energy expenditure in abdominal white adipose tissue and glucose utilization in muscle

Cross-Platform Comparison of Untargeted and Targeted Lipidomics Approaches on Aging Mouse Plasma.

Lipidomics - the global assessment of lipids - can be performed using a variety of mass spectrometry (MS)-based approaches. However, choosing the optimal approach in terms of lipid coverage, robustness and throughput can be a challenging task. Here, we compare a novel targeted quantitative lipidomics platform known as the Lipidyzer to a conventional untargeted liquid chromatography (LC)-MS approach. We find that both platforms are efficient in profiling more than 300 lipids across 11 lipid classes in mouse plasma with precision and accuracy below 20% for most lipids. While the untargeted and targeted platforms detect similar numbers of lipids, the former identifies a broader range of lipid classes and can unambiguously identify all three fatty acids in triacylglycerols (TAG). Quantitative measurements from both approaches exhibit a median correlation coefficient (r) of 0.99 using a dilution series of deuterated internal standards and 0.71 using endogenous plasma lipids in the context of aging. Application of both platforms to plasma from aging mouse reveals similar changes in total lipid levels across all major lipid classes and in specific lipid species. Interestingly, TAG is the lipid class that exhibits the most changes with age, suggesting that TAG metabolism is particularly sensitive to the aging process in mice. Collectively, our data show that the Lipidyzer platform provides comprehensive profiling of the most prevalent lipids in plasma in a simple and automated manner

Large D/H variations in bacterial lipids reflect central metabolic pathways

Large hydrogen-isotopic (D/H) fractionations between lipids and growth water have been observed in most organisms studied to date. These fractionations are generally attributed to isotope effects in the biosynthesis of lipids, and are frequently assumed to be approximately constant for the purpose of reconstructing climatic variables. Here, we report D/H fractionations between lipids and water in 4 cultured members of the phylum Proteobacteria, and show that they can vary by up to 500‰ in a single organism. The variation cannot be attributed to lipid biosynthesis as there is no significant change in these pathways between cultures, nor can it be attributed to changing substrate D/H ratios. More importantly, lipid/water D/H fractionations vary systematically with metabolism: chemoautotrophic growth (approximately −200 to −400‰), photoautotrophic growth (−150 to −250‰), heterotrophic growth on sugars (0 to −150‰), and heterotrophic growth on TCA-cycle precursors and intermediates (−50 to +200‰) all yield different fractionations. We hypothesize that the D/H ratios of lipids are controlled largely by those of NADPH used for biosynthesis, rather than by isotope effects within the lipid biosynthetic pathway itself. Our results suggest that different central metabolic pathways yield NADPH—and indirectly lipids—with characteristic isotopic compositions. If so, lipid δD values could become an important biogeochemical tool for linking lipids to energy metabolism, and would yield information that is highly complementary to that provided by ^(13)C about pathways of carbon fixation