Effects of fatty acids on T cell function: role in atherosclerosis

Fatty acids affect the pathogenesis of atherosclerosis, and accumulating evidence shows that fatty acids also modulate T cell functions and processes. This Review summarizes the effects of circulating fatty acids on the metabolism, activation, proliferation and polarization of T cells and how these changes influence the subsequent functions of T cells in the pathogenesis of atherosclerosis.T cells are among the most common cell types present in atherosclerotic plaques and are increasingly being recognized as a central mediator in atherosclerosis development and progression. At the same time, triglycerides and fatty acids have re-emerged as crucial risk factors for atherosclerosis. Triglycerides and fatty acids are important components of the milieu to which the T cell is exposed from the circulation to the plaque, and increasing evidence shows that fatty acids influence T cell function. In this Review, we discuss the effects of fatty acids on four components of the T cell response - metabolism, activation, proliferation and polarization - and the influence of these changes on the pathogenesis of atherosclerosis. We also discuss how quiescent T cells can undergo a type of metabolic reprogramming induced by exposure to fatty acids in the circulation that influences the subsequent functions of T cells after activation, such as in atherosclerotic plaques.Cardiolog

Latitudinal Variance in the Drivers and Pacing of Warmth During Mid-Pleistocene MIS 31 in the Antarctic Zone of the Southern Ocean

Early Pleistocene Marine Isotope Stage (MIS)-31 (1.081–1.062 Ma) is a unique interval of extreme global warming, including evidence of a West Antarctic Ice Sheet (WAIS) collapse. Here we present a new 1,000-year resolution, spanning 1.110–1.030 Ma, diatom-based reconstruction of primary productivity, relative sea surface temperature changes, sea-ice proximity/open ocean conditions and diatom species absolute abundances during MIS-31, from the Scotia Sea (59°S) using deep-sea sediments collected during International Ocean Discovery Program (IODP) Expedition 382. The lower Jaramillo magnetic reversal (base of C1r.1n, 1.071 Ma) provides a robust and independent time-stratigraphic marker to correlate records from other drill cores in the Antarctic Zone of the Southern Ocean (AZSO). An increase in open ocean species Fragilariopsis kerguelensis in early MIS-31 at 53°S (Ocean Drilling Program Site 1,094) correlates with increased obliquity forcing, whereas at 59°S (IODP Site U1537; this study) three progressively increasing, successive peaks in the relative abundance of F. kerguelensis correlate with Southern Hemisphere-phased precession pacing. These observations reveal a complex pattern of ocean temperature change and sustained sea surface temperature increase lasting longer than a precession cycle within the Atlantic sector of the AZSO. Timing of an inferred WAIS collapse is consistent with delayed warmth (possibly driven by sea-ice dynamics) in the southern AZSO, supporting models that indicate WAIS sensitivity to local sub-ice shelf melting. Anthropogenically enhanced impingement of relatively warm water beneath the ice shelves today highlights the importance of understanding dynamic responses of the WAIS during MIS-31, a warmer than Holocene interglacial.Postprin

Episodes of Early Pleistocene West Antarctic Ice Sheet Retreat Recorded by Iceberg Alley Sediments

Ice loss in the Southern Hemisphere has been greatest over the past 30 years in West Antarctica. The high sensitivity of this region to climate change has motivated geologists to examine marine sedimentary records for evidence of past episodes of West Antarctic Ice Sheet (WAIS) instability. Sediments accumulating in the Scotia Sea are useful to examine for this purpose because they receive iceberg-rafted debris (IBRD) sourced from the Pacific- and Atlantic-facing sectors of West Antarctica. Here we report on the sedimentology and provenance of the oldest of three cm-scale coarse-grained layers recovered from this sea at International Ocean Discovery Program Site U1538. These layers are preserved in opal-rich sediments deposited ∼1.2 Ma during a relatively warm regional climate. Our microCT-based analysis of the layer's in-situ fabric confirms its ice-rafted origin. We further infer that it is the product of an intense but short-lived episode of IBRD deposition. Based on the petrography of its sand fraction and the Phanerozoic 40Ar/39Ar ages of hornblende and mica it contains, we conclude that the IBRD it contains was likely sourced from the Weddell Sea and/or Amundsen Sea embayment(s) of West Antarctica. We attribute the high concentrations of IBRD in these layers to “dirty” icebergs calved from the WAIS following its retreat inland from its modern grounding line. These layers also sit at the top of a ∼366-m thick Pliocene and early Pleistocene sequence that is much more dropstone-rich than its overlying sediments. We speculate this fact may reflect that WAIS mass-balance was highly dynamic during the ∼41-kyr (inter)glacial world.Postprin

Antiphased dust deposition and productivity in the Antarctic Zone over 1.5 million years

The Southern Ocean paleoceanography provides key insights into how iron fertilization and oceanic productivity developed through Pleistocene ice-ages and their role in influencing the carbon cycle. We report a high-resolution record of dust deposition and ocean productivity for the Antarctic Zone, close to the main dust source, Patagonia. Our deep-ocean records cover the last 1.5 Ma, thus doubling that from Antarctic ice-cores. We find a 5 to 15-fold increase in dust deposition during glacials and a 2 to 5-fold increase in biogenic silica deposition, reflecting higher ocean productivity during interglacials. This antiphasing persisted throughout the last 25 glacial cycles. Dust deposition became more pronounced across the Mid-Pleistocene Transition (MPT) in the Southern Hemisphere, with an abrupt shift suggesting more severe glaciations since ~0.9 Ma. Productivity was intermediate pre-MPT, lowest during the MPT and highest since 0.4 Ma. Generally, glacials experienced extended sea-ice cover, reduced bottom-water export and Weddell Gyre dynamics, which helped lower atmospheric CO2 levels.Postprin

Oleic acid triggers metabolic rewiring of T cells poising them for T helper 9 differentiation

T cells are the most common immune cells in atherosclerotic plaques, and the function of T cells can be altered by fatty acids. Here, we show that pre-exposure of CD4+ T cells to oleic acid, an abundant fatty acid linked to cardiovascular events, upregulates core metabolic pathways and promotes differentiation into interleukin-9 (IL-9)-producing cells upon activation. RNA sequencing of non-activated T cells reveals that oleic acid upregulates genes encoding key enzymes responsible for cholesterol and fatty acid biosynthesis. Transcription footprint analysis links these expression changes to the differentiation toward TH9 cells, a pro-atherogenic subset. Spectral flow cytometry shows that pre-exposure to oleic acid results in a skew toward IL-9+-producing T cells upon activation. Importantly, pharmacological inhibition of either cholesterol or fatty acid biosynthesis abolishes this effect, suggesting a beneficial role for statins beyond cholesterol lowering. Taken together, oleic acid may affect inflammatory diseases like atherosclerosis by rewiring T cell metabolism.</p

Data report: calcareous nannofossils and lithologic constraints on the age model of IODP Site U1450, Expedition 354, Bengal Fan

International audienc