Soluble CD163 is not increased in visceral fat and steatotic liver and is even suppressed by free fatty acids in vitro

Visceral fat differs from subcutaneous fat by higher local inflammation and increased release of IL-6 and free fatty acids (FFA) which contribute to hepatic steatosis. IL-6 has been shown to upregulate the monocyte/macrophage specific receptor CD163 whose soluble form, sCD163, is increased in inflammatory diseases. Here, it was analyzed whether CD163 and sCD163 are differentially expressed in the human fat depots and fatty liver. CD163 mRNA and protein were similarly expressed in paired samples of human visceral and subcutaneous fat, and comparable levels in portal venous and systemic venous blood of liver-healthy controls indicate that release of sCD163 from visceral adipose tissue was not increased. CD163 was also similarly expressed in steatotic liver when compared to non-steatotic tissues and sCD163 was almost equal in the respective sera. Concentrations of sCD163 were not affected when passing the liver excluding substantial hepatic removal/release of this protein. A high concentration of IL-6 upregulated CD163 protein while physiological doses had no effect. However, sCD163 was not increased by any of the IL-6 doses tested. FFA even modestly decreased CD163 and sCD163. The anti-inflammatory mediators fenofibrate, pioglitazone, and eicosapentaenoic acid (EPA) did not influence sCD163 levels while CD163 was reduced by EPA. These data suggest that in humans neither visceral fat nor fatty liver are major sources of sCD163.

Transforming growth factor-beta inhibits the expression of clock genes

Disturbances of sleep-wake rhythms are an important problem in Alzheimer's disease (AD). Circadian rhythms are regulated by clock genes. Transforming growth factor-beta (TGF-β) is overexpressed in neurons in AD and is the only cytokine that is increased in cerebrospinal fluid (CSF). Our data show that TGF-β2 inhibits the expression of the clock genes Period (Per)1, Per2, and Rev-erbα, and of the clock-controlled genes D-site albumin promoter binding protein (Dbp) and thyrotroph embryonic factor (Tef). However, our results showed that TGF-β2 did not alter the expression of brain and muscle Arnt-like protein-1 (Bmal1). The concentrations of TGF-β2 in the CSF of 2 of 16 AD patients and of 1 of 7 patients with mild cognitive impairment were in the dose range required to suppress the expression of clock genes. TGF-β2-induced dysregulation of clock genes may alter neuronal pathways, which may be causally related to abnormal sleep-wake rhythms in AD patients.

On the comparison of VR-responses, as performance measures in prospective memory, with auditory P300 responses in MCI detection

Patients with amnestic mild cognitive impairment are at high risk for developing Alzheimer's disease. Besides episodic memory dysfunction they show deficits in accessing contextual knowledge that further specifies a general spatial navigation task or an executive function (EF) virtual action planning. There has been only one previous work with virtual reality and the use of a virtual action planning supermarket for the diagnosis of mild cognitive impairment. The authors of that study examined the feasibility and the validity of the virtual action planning supermarket (VAP-S) for the diagnosis of patients with mild cognitive impairment (MCI) and found that the VAP-S is a viable tool to assess EF deficits. In our study we employed the in-house platform of virtual action planning museum (VAP-M) and a sample of 25 MCI and 25 controls, in order to investigate deficits in spatial navigation, prospective memory and executive function. In addition, we used the morphology of late components in event-related potential (ERP) responses, as a marker for cognitive dysfunction. The related measurements were fed to a common classification scheme facilitating the direct comparison of both approaches. Our results indicate that both the VAP-M and ERP averages were able to differentiate between healthy elders and patients with amnestic mild cognitive impairment and agree with the findings of the virtual action planning supermarket (VAP-S). The sensitivity (specificity) was 100% (98%) for the VAP-M data and 87%(90%) for the ERP responses. Considering that ERPs have proven to advance the early detection and diagnosis of "presymptomatic AD", the suggested VAP-M platform appears as an appealing alternative.

Milk fatty acids as possible biomarkers to early diagnose elevated concentrations of blood plasma nonesterified fatty acids in dairy cows

Most cows encounter a state of negative energy balance during the periparturient period, which may lead to metabolic disorders and impaired fertility. The aim of this study was to assess the potential of milk fatty acids as diagnostic tools of detrimental levels of blood plasma nonesterified fatty acids (NEFA), defined as NEFA concentrations beyond 0.6 mmol/L, in a data set of 92 early lactating cows fed a glucogenic or lipogenic diet and subjected to 0-, 30-, or 60-d dry period before parturition. Milk was collected in wk 2, 3, 4, and 8 (n = 368) and blood was sampled weekly from wk 2 to 8 after parturition. Milk was analyzed for milk fatty acids and blood plasma for NEFA. Data were classified as "at risk of detrimental blood plasma NEFA" (NEFA ≥ 0.6 mmol/L) and "not at risk of detrimental blood plasma NEFA" (NEFA <0.6 mmol/L). Concentrations of 45 milk fatty acids and milk fat C18:1 cis-9-to-C15:0 ratio were subjected to a discriminant analysis. Milk fat C18:1 cis-9 revealed the most discriminating variable to identify detrimental blood plasma NEFA. A false positive rate of 10% allowed us to diagnose 46% of the detrimental blood plasma NEFA cases based on a milk fat C18:1 cis-9 concentration of at least 230 g/kg of milk fatty acids. Additionally, it was assessed whether the milk fat C18:1 cis-9 concentrations of wk 2 could be used as an early warning for detrimental blood plasma NEFA risk during the first 8 wk in lactation. Cows with at least 240 g/kg of C18:1 cis-9 in milk fat had about 50% chance to encounter blood plasma NEFA values of 0.6 mmol/L or more during the first 8 wk of lactation, with a false positive rate of 11.4%. Profit simulations were based on costs for cows suffering from detrimental blood plasma NEFA, and costs for preventive treatment based on daily dosing of propylene glycol for 3 wk. Given the relatively low incidence rate (8% of all observations), continuous monitoring of milk fatty acids during the first 8 wk of lactation to diagnose detrimental blood plasma NEFA does not seem cost effective. On the contrary, milk fat C18:1 cis-9 of the second lactation week could be an early warning of cows at risk of detrimental blood NEFA. In this case, selective treatment may be cost effective.

Oral Lutein Supplementation Enhances Macular Pigment Density and Contrast Sensitivity but Not in Combination With Polyunsaturated Fatty Acids.

Purpose It has been shown that lutein and zeaxanthin accumulate in the macula where they enhance contrast sensitivity and may reduce the risk of progression to advanced age-related macular degeneration (AMD). Furthermore, omega-3 long-chain polyunsaturated fatty acids (PUFA) might further reduce this risk. However, controversy exists regarding whether PUFA may reduce the bioavailability of lutein. Methods This was a prospective 12-month, randomized, open label study evaluating the effect of supplementation with lutein, other antioxidants, and minerals on contrast sensitivity (CS) and macular pigment optical density (MPOD) in patients with age-related maculopathy. A total of 79 patients were randomized to either lutein (10 mg) and antioxidant supplement or lutein and antioxidant supplement in combination with PUFA. Patients received supplementation for a period of 6 months and were followed for a total of 12 months. Results Serum lutein and zeaxanthin increased significantly by the first follow-up visit at 1 month, and remained elevated throughout the intervention period of 6 months in the lutein-only group but not in the lutein+PUFA group. Macular pigment optical density and CS increased significantly in the lutein-only group (P < 0.005) but not in the lutein+PUFA group (P = 0.059) compared to baseline. Best-corrected visual acuity remained unchanged during the entire study period in both groups. Conclusions Addition of PUFA may reduce the bioavailability of lutein and therefore lessen the beneficial effect on macular pigment and CS. This needs to be considered when prescribing lutein supplements to patients with low lutein levels. (ClinicalTrials.gov number, NCT00563979.).

Diagnosing the Prodromal State of Alzheimer's Disease

Mild Cognitive Impairment- Amnestic Subtype (MCIa) is a putative prodromal stage of Alzheimer’s Disease (AD) characterized by focal deficits in episodic verbal memory. Less is known about relative deficits in visuospatial learning, although there is ample evidence indicating involvement of the hippocampus in visuospatial learning, as well as hippocampal degeneration in early AD. The aim of this study was to better characterize the components of working memory dysfunction in people with MCIa to increase the ability to reliably diagnose this disease. Fifty-six elderly adults diagnosed with MCIa and 94 healthy elderly completed a hidden maze learning task. Results indicated similar functioning between groups on measures of reasoning, problem solving, and accuracy. However, MCIa subjects were less efficient at learning the hidden path, making more errors per second on average (Cohen’s d= -.78) and requiring a longer time to complete the maze (Cohen’s d=.77). The learning curve between the first two trials was four times as steep for healthy elderly compared to MCIa (slopes = 4.9 vs. 1.24, respectively), indicating that MCIa subjects exhibited relative difficulty in holding and making effective use of an internal spatial map in order to improve performance. Our results suggest that MCIa patients have focal deficits in visuospatial working memory, with relative preservation of functioning on other more global measures of cognitive functioning. This particular pattern of results may be specific to the amnestic variant of MCI.

n-fatty acids of shale partings in the Franciscan bedded cherts

Normal saturated fatty acid (n-fatty acid) in marine sediments from coastal and pelagic environments were analyzed. The coastal sediments contain both short-chained n-fatty acids with carbon numbers from 12 to 18 and long-chained acids from 22 to 32, whereas the pelagic sediments contain predominantly short-chained acids. The relative abundance of short-chained to long-chained n-fatty acids, expressed by the molar ratio C16/C26, can be an indicator to assess the depositional environment of sedimentary rocks. The ratio of long-chained n-fatty acids (C22-C32) to the total n-fatty acids also has the potential to discriminate sedimentary environments. The indicators based on the n-fatty acids were applied to the Franciscan bedded cherts. The result shows that the bedded cherts had deposited in continuous environments from the pelagic to the coastal. This is in harmony with the same inference based on major, trace and rare earth elements and normal paraffins.

Fatty acids and intact polar lipids of laminated microbial sediments from St. Peter Ording, German Wadden Sea

Hidden for the untrained eye through a thin layer of sand, laminated microbial sediments occur in supratidal beaches along the North Sea coast. The inhabiting microbial communities organize themselves in response to vertical gradients of light, oxygen or sulfur compounds. We performed a fine-scale investigation on the vertical zonation of the microbial communities using a lipid biomarker approach, and assessed the biogeochemical processes using a combination of microsensor measurements and a 13C-labeling experiment. Lipid biomarker fingerprinting showed the overarching importance of cyanobacteria and diatoms in these systems, and heterocyst glycolipids revealed the presence of diazotrophic cyanobacteria even in 9 to 20 mm depth. High abundance of ornithine lipids (OL) throughout the system may derive from sulfate reducing bacteria, while a characteristic OL profile between 5 and 8 mm may indicate presence of purple non-sulfur bacteria. The fate of 13C-labeled bicarbonate was followed by experimentally investigating the uptake into microbial lipids, revealing an overarching importance of cyanobacteria for carbon fixation. However, in deeper layers, uptake into purple sulfur bacteria was evident, and a close microbial coupling could be shown by uptake of label into lipids of sulfate reducing bacteria in the deepest layer. Microsensor measurements in sediment cores collected at a later time point revealed the same general pattern as the biomarker analysis and the labeling experiments. Oxygen and pH-microsensor profiles showed active photosynthesis in the top layer. The sulfide that diffuses from deeper down and decreases just below the layer of active oxygenic photosynthesis indicates the presence of sulfur bacteria, like anoxygenic phototrophs that use sulfide instead of water for photosynthesis.

Carbon isotopic compositions and concentrations of major fatty acids in the Beggiatoa covered sediment core at the crest of southern Hydrate Ridge

Membrane fatty acids were extracted from a sediment core above marine gas hydrates at Hydrate Ridge, NE Pacific. Anaerobic sediments from this environment are characterized by high sulfate reduction rates driven by the anaerobic oxidation of methane (AOM). The assimilation of methane carbon into bacterial biomass is indicated by carbon isotope values of specific fatty acids as low as -103 per mill. Specific fatty acids released from bacterial membranes include C 16:1 omega 5c , C 17:1 omega 6c , and cyC 17:0 omega 5,6 , all of which have been fully characterized by mass spectrometry. These unusual fatty acids continuously display the lowest d13 C values in all sediment horizons and two of them are detected in high abundance (i.e., C 16:1 omega 5c and cyC 17:0 omega 5,6 ). Combined with microscopic examination by fluorescence in situ hybridization specifically targeting sulfate-reducing bacteria (SRB) of the Desulfosarcina/Desulfococcus group, which are present in the aggregates of AOM consortia in extremely high numbers, these specific fatty acids appear to provide a phenotypic fingerprint indicative for SRB of this group. Correlating depth profiles of specific fatty acid content and aggregate number in combination with pore water sulfate data provide further evidence of this finding. Using mass balance calculations we present a cell-specific fatty acid pattern most likely displaying a very close resemblance to the still uncultured Desulfosarcina/Desulfococcus species involved in AOM.

Fatty acids, alcohols and hydrocarbons of microbial mats from Lake 2A on Kiritimati Island

Modern microbial mats are widely recognized as useful analogs for the study of biogeochemical processes relevant to paleoenvironmental reconstruction in the Precambrian. We combined microscopic observations and investigations of biomarker composition to investigate community structure and function in the upper layers of a thick phototrophic microbial mat system from a hypersaline lake on Kiritimati (Christmas Island) in the Northern Line Islands, Republic of Kiribati. In particular, an exploratory incubation experiment with 13C-labeled bicarbonate was conducted to pinpoint biomarkers from organisms actively fixing carbon. A high relative abundance of the cyanobacterial taxa Aphanocapsa and Aphanothece was revealed by microscopic observation, and cyanobacterial fatty acids and hydrocarbons showed 13C-uptake in the labeling experiment. Microscopic observations also revealed purple sulfur bacteria (PSB) in the deeper layers. A cyclic C19:0 fatty acid and farnesol were attributed to this group that was also actively fixing carbon. Background isotopic values indicate Calvin-Benson cycle-based autotrophy for cycC19:0 and farnesol-producing PSBs. Biomarkers from sulfate-reducing bacteria (SRB) in the top layer of the mat and their 13C-uptake patterns indicated a close coupling between SRBs and cyanobacteria. Archaeol, possibly from methanogens, was detected in all layers and was especially abundant near the surface where it contained substantial amounts of 13C-label. Intact glycosidic tetraether lipids detected in the deepest layer indicated other archaea. Large amounts of ornithine and betaine bearing intact polar lipids could be an indicator of a phosphate-limited ecosystem, where organisms that are able to substitute these for phospholipids may have a competitive advantage.

Elemental contents, non-carbonate, fatty acids and alcohols analysis from different Holes of IODP Expedition 310

During IODP Expedition 310 (Tahiti Sea Level), drowned Pleistocene-Holocene barrier-reef terraces were drilled on the slope of the volcanic island. The deglacial reef succession typically consists of a coral framework encrusted by coralline algae and later by microbialites; the latter make up < 80% of the rock volume. Lipid biomarkers were analyzed in order to identify organisms involved in reef-microbialite formation at Tahiti, as the genesis of deglacial microbialites and the conditions favoring their formation are not fully understood. Sterols plus saturated and monounsaturated short-chain fatty acids predominantly derived from both marine primary producers (algae) and bacteria comprise 44 wt% of all lipids on average, whereas long-chain fatty acids and long-chain alcohols derived from higher land plants represent an average of only 24 wt%. Bacterially derived mono-O-alkyl glycerol ethers (MAGEs) and branched fatty acids (10-Me-C16:0; iso- and anteiso-C15:0 and -C17:0) are exceptionally abundant in the microbial carbonates (average, 19 wt%) and represent biomarkers of intermediate-to-high specificity for sulfate-reducing bacteria. Both are relatively enriched in 13C compared to eukaryotic lipids. No lipid biomarkers indicative of cyanobacteria were preserved in the microbialites. The abundances of Al, Si, Fe, Mn, Ba, pyroxene, plagioclase, and magnetite reflect strong terrigenous influx with Tahitian basalt as the major source. Chemical weathering of the basalt most likely elevated nutrient levels in the reefs and this fertilization led to an increase in primary production and organic matter formation, boosting heterotrophic sulfate reduction. Based on the observed biomarker patterns, sulfate-reducing bacteria were apparently involved in the formation of microbialites in the coral reefs off Tahiti during the last deglaciation.

Occurrence of metazoans, and gut pigments and fatty acid composition of Acartia bifilosa in ice and under-ice water samples from Santala Bay

A field study was conducted in Santala Bay with weekly samplings during February and March 2000. Ice thickness was 20-28 cm, snow cover 0-1 cm. The under-ice water column was stratified with a cold (-0.3 - 0.2°C) and less saline (S = 2.1-4.9) interface layer. Concentrations of particulate organic carbon (0.5-5.8 mg POC/l) and algal pigments (0.3-18.2 µg chlorophyll a/l) were higher in the ice than in the water (0.2-0.5 mg POC/l, 1.6-7.1 µg chlorophyll a/l) and peaked mostly in the bottom part of the ice. The thin ice and almost lacking snow cover had favoured an early ice-algal and phytoplankton bloom. The diversity of metazoans was low, with six species in the ice and eight species in the under-ice water. The rotifer Synchaeta cf. littoralis dominated both in ice and water, with maximum abundances of 230 individuals/l in the bottom part of the ice. Rotifer eggs were also observed in the ice. Baltic sea ice seems to be a suitable habitat for rotifers. Nauplii and copepodids of the calanoid Acartia longiremis in the under-ice water showed some herbivorous feeding (<0.1-0.23 ng gut pigment/individual), but analysis of fatty acids, fatty alcohols and biomarker ratios indicated a more omnivorous/carnivorous diet. Despite low temperatures, this copepod showed growth and development below the ice, doubling in numbers (mainly CI, CII) from 118 to 230 individuals m during the third week of March.

Water chemistry, and isotopic ratios and fatty acids and alcohols in Calanus finmarchicus CV, norther Mid-Atlantic Ridge

Fatty acid and alcohol profiles and stable nitrogen and carbon isotope values, d15N and d13C, of Calanus finmarchicus CV were studied in June 2004 to estimate their trophic status along the northern Mid-Atlantic Ridge i.e. the Reykjanes Ridge (RR), extending from Iceland in the north to the productive region of the Sub-Polar Front (SPF) in the south. Two main groups of stations were defined in the study area based on fatty acid (FA) and fatty alcohol compositions, the stations in the RR area constituted one group and the stations in the frontal area constituted another. The sum of relative amounts of the dietary FAs was significantly higher in the RR area than in the frontal area. Conversely, the long-chained FAs, 20:1 and 22:1, were found in significantly lower relative amounts in the RR area than in the frontal area, thus indicating later ascent of the animals in the frontal area. Further support of this is provided by the fatty alcohols ratio 20:1/22:1 which differed significantly between the two areas. The d15N values were significantly higher in the frontal area compared to the RR area indicating higher trophic position and/or different pelagic-POM baseline in these areas.

Seasonal fatty acid and fatty alcohol composition of Pseudocalanus minutus and Oithona similis in Kongsfjorden (Svalbard)

Seasonal lipid dynamics of various developmental stages were investigated in Pseudocalanus minutus and Oithona similis. For P. minutus, the dominance of 16:1(n?7), 16:4(n?3) and 20:5(n?3) fatty acids indicated a diatom-based nutrition in spring, whereas 22:6(n?3), 16:0, 18:2(n?6) and 18:1(n?9) pointed to a flagellate-based diet during the rest of the year as well as omnivorous/carnivorous low-level feeding during winter. The shorter-chain fatty alcohols 14:0 and 16:0 prevailed, also reflecting biosynthetic processes typical of omnivores or carnivores. Altogether, the lipid signatures characterized P. minutus as an opportunistic feeder. In contrast, O. similis had consistently high amounts of the 18:1(n?9) fatty acid in all stages and during all seasons pointing to a generally omnivorous/carnivorous/detritivorous diet. Furthermore, the fatty alcohol 20:1(n?9) reached high percentages especially in adult females and males, and feeding on Calanus faecal pellets is suggested. Fatty alcohols, as wax ester moieties, revealed significant seasonal variations in O. similis and a seasonal trend towards wax ester accumulation in autumn in P. minutus. P. minutus utilized its lipid deposits for development in the copepodite stages III and IV and for gonad maturation in CV and females during the dark season. However, CVs and females depended on the spring phytoplankton bloom for final maturation processes and reproduction. O. similis fueled gonad maturation and egg production for reproduction in June by wax esters, whereas reproduction in August/September co-occurred with the accumulation of new depot lipids. Both species revealed significantly higher wax ester levels in deeper (>50 m) as compared to surface (0-50 m) dwelling individuals related to a descent prior to overwintering.