Endothelial lipase and the metabolic syndrome

PURPOSE OF REVIEW: Several in-vitro and in-vivo animal studies indicate that endothelial lipase plays a key role in the intravascular remodeling of lipoproteins, particularly HDL. This review integrates this body of knowledge with more recent data in humans linking endothelial lipase to HDL metabolism and other features of the metabolic syndrome. RECENT FINDINGS: Human studies generally support the involvement of endothelial lipase in modulating plasma HDL. The association between endothelial lipase and metabolism of apolipoprotein B-containing lipoproteins in humans, however, has not been entirely consistent with previous findings in vitro and in animals. Finally, elevated plasma endothelial lipase has been associated with abdominal obesity and hypertension, and there is now compelling evidence that inflammation and in-vivo regulation of endothelial lipase may be intrinsically related. SUMMARY: Accumulating evidence indicates that endothelial lipase plays a role in the etiology of the atherogenic plasma lipoprotein profile characteristic of the metabolic syndrome. Increased endothelial lipase activity is linked to the underlying proinflammatory state in this condition. Further studies are required, however, to define the extent to which endothelial lipase contributes to the dyslipidemia of the metabolic syndrome relative to other important regulating factors, such as lipoprotein lipase, hepatic lipase, and cholesterol ester transfer protein.     

Apolipoprotein A-I, A-II, and VLDL-B-100 metabolism in men: comparison of a low-fat diet and a high-monounsaturated fatty acid diet

The impact of a low-fat diet and a high-MUFA diet on apolipoprotein A-I (apoA-I), apoA-II, and VLDL-apoB-100 metabolism in conditions of unrestricted (ad libitum) energy intake was compared in 65 men randomly assigned to one of two predefined experimental diets. A subsample of 18 men participated in the kinetic study. Before and after the 6-7 week dietary intervention, kinetic subjects received a primed-constant infusion of [5,5,5-2H3]L-leucine for 12 h under feeding conditions. ApoA-I production rate (PR; -31.5%; P <0.001) and fractional catabolic rate (FCR; -24.3%; P <0.05) were significantly decreased after the low-fat diet. These changes in apoA-I PR and FCR with the low-fat diet were also significantly different from those observed with the high-MUFA diet (P <0.01 and P <0.05, respectively). ApoA-II FCR was significantly increased in the high-MUFA group only. No significant within- or between-diet difference was found in VLDL-apoB-100 PR or FCR. These results emphasize the differential impact of the low-fat diet and high-MUFA diet on HDL metabolism.     

Endothelial lipase is associated with inflammation in humans

The aim of this study was to investigate the extent to which inflammation is linked with plasma endothelial lipase (EL) concentrations among healthy sedentary men. Plasma C-reactive protein (CRP) concentrations were measured with a highly sensitive commercial immunoassay, plasma interleukin-6 (IL-6) concentrations were measured using a commercial ELISA, and plasma secretory phospholipase A(2) type IIA (sPLA(2)-IIA) concentrations were measured using a commercial assay in a sample of 74 moderately obese men (mean body mass index, 29.8 +/- 5.2 kg/m(2)). Plasma EL concentrations were positively correlated with various indices of obesity, fasting plasma insulin, and plasma CRP, IL-6, and sPLA(2)-IIA concentrations. Multiple regression analyses revealed that plasma CRP concentrations explained 14.5% (P = 0.0008) of the variance in EL concentrations. When entered into the model, LPL activity accounted for 16.1% (P < 0.0001) and plasma CRP concentrations accounted for 20.9% (P < 0.0001) of the variance in EL concentrations. The combined impact of visceral adipose tissue (VAT) and of an inflammation score on EL concentrations was investigated. Among subjects with high or low VAT, those having a high inflammation score based on plasma CRP, IL-6, and sPLA(2)-IIA concentrations had increased plasma EL concentrations (P = 0.0005). In conclusion, our data reveal a strong association between proinflammatory cytokines and plasma EL concentrations among healthy people with low or high VAT levels.     

Re-awakening dormant life history variation: stable isotopes indicate anadromy in bull trout following dam removal on the Elwha River,Washington

Migratory species take advantage of multiple habitats during their life cycle to optimize growth, survival, and reproduction. However, migration also makes them vulnerable to habitat degradation and exploitation in each habitat, and loss of connection between habitats. Partially migratory species (i.e., migration is facultative rather than obligate) can persist after loss of connectivity and may then resume migration after the habitats are reconnected. We analyzed stable isotopes of carbon and nitrogen to investigate the possible use of marine habitats for foraging by bull trout, Salvelinus confluentus, in years immediately after removal of impassable hydroelectric dams on the Elwha River, Washington State, USA. Juveniles in the Elwha River estuary were similar in δ¹⁵N and δ¹³C values to those in the estuary of the free-flowing Dungeness River nearby, and the values of fish from the estuaries were higher than those of juveniles collected in the river, consistent with use of marine food sources. Adult bull trout collected in each of the rivers had values indicating extensive reliance on marine prey - similar to those of adult Pacific salmon that had spent several years at sea. Taken together, these data demonstrate that the Elwha River bull trout, almost entirely landlocked for a century, are rapidly resuming anadromy and that the marine prey contribute substantially to their trophic ecology and likely their growth. More broadly, the results reveal the importance of connectivity for migratory fishes, their ability to resume anadromy once the connection between habitats is restored, and the population resilience that partial migration provides for them.     

Management of the margins in cutover bogs: ecological conditions and effects of afforestation

Several studies contributed to the development of restoration techniques for open Sphagnum-dominated habitats on peat-extracted bogs. Yet, in exception to some afforestation efforts, connectivity between restored sites and surrounding landscapes has received little attention. The general goal of this study is to ameliorate management of very shallow peat fields (<30 cm) located within the margins of peat-extracted bogs. Firstly, to assist decision making in peatland management, baseline ecological conditions, peat physicochemistry and spontaneous vegetation recolonization were assessed for 18 of these fields. This first study revealed that (1) concentrations of several macro-nutrients are almost one order of magnitude lower for unrestored fields than previously characterized natural lagg habitats of the same region, and (2) there is little spontaneous colonization. In a second study, peat chemistry and soil/air microclimate were evaluated in plantations established on shallow residual peat (a 21-year-old Larix laricina plantation and an 18-year-old Picea mariana plantation) and compared to adjacent unrestored shallow bare-peat fields. This second study showed that afforested peat fields are characterized by (1) a soil enriched in nutrients, notably in N, P, and K, and (2) a more humid and cooler microclimate at the soil/air interface, with less daily humidity and temperature fluctuations. These results indicate that afforestation is an appropriate approach to start an ecological recovery. Yet, the absence of natural recolonization by herbs and mosses in the understory of afforested peat fields suggests that reintroduction of appropriate understory species should also be considered if the goal is to restore a fully functional ecosystem.     

The anti-tumor activity of anti-CTLA-4 is mediated through its induction of IFNγ

The T-cell-specific receptor, CTLA-4, has been demonstrated to be a potent negative regulator of lymphocyte activation, the functional significance of which has been demonstrated in murine tumor models using blocking antibodies. However, the mechanism(s) involved in enhancing tumor regression has not been identified. In this study, we determined whether IFN gamma was playing a role in this activity. In vitro, anti-CTLA-4 enhanced IFN gamma production by lymph node cells obtained from tumor-bearing mice (351 pg/ml vs 77 pg/ml). Additionally, fibrosarcoma-challenged animals treated with anti-CTLA-4 had elevated levels of the IFN-inducible enzyme 2-5-OAS in draining lymph nodes (850 pM vs 260 pM for controls) and an increased amount of IFN gamma in tumor lysates (at day 7, 620 pg/100 micrograms vs 160 pg/100 micrograms in controls). The importance of IFN gamma was demonstrated by the ability of neutralizing antibodies to completely abrogate the anti-tumor effects of anti-CTLA-4. Moreover, fibrosarcoma cells were shown to be exquisitely sensitive to IFN gamma-mediated class I upregulation and histological examination of tumors from anti-CTLA-4-treated mice revealed a trend toward increased tumor cell apoptosis and decreased angiogenesis. These studies have demonstrated that one mechanism for the anti-tumor effects of anti-CTLA-4 relates to its ability to augment IFN gamma production, resulting in an increased expression of class I on the tumor, enhanced apoptosis, and a decrease in blood vessel growth.     

Effects of Recreation and Hunting on Flushing Distance of Capercaillie

Abstract: The capercaillie (Tetrao urogallus) in Central Europe is an endangered species of grouse that is thought to be highly susceptible to human disturbance, possibly causing local populations to decline. We investigated the behavioral response of capercaillie in the Black Forest, Germany, and the French Pyrenees to an off-trail hiker by measuring flushing distances. Flushing distance varied with capercaillie sex, visibility of the hiker, intensity of winter tourism, and hunting pressure. Independent of the study area, males flushed at consistently longer distances than females, and lower visual blocking between bird and hiker resulted in longer flushing distances. Capercaillie flew at longer distances from an approaching hiker in areas with high intensity of winter tourism or hunting pressure than in undisturbed areas. We recommend the establishment of regulations requiring hikers to stay on trails and to close trails where intertrail distances fall below 100 m (90% of all flushing events appeared within 50 m). Furthermore, planting or preserving evergreen conifer trees in dense rows along critical parts of disturbance sources, reducing the degree of visibility between capercaillie and recreationists would increase habitat for capercaillie in forests with predictable recreation activities.     

Effects of the type of meniscal lesion on knee function

The relationship between the type of meniscal lesion (bucket-handle, flap or degenerative tears) and preoperative knee function (5.1±6.2 days before arthroscopic meniscectomy) was studied in 35 patients. Patients with bucket-handle tears (group B, n=12) had large knee extension work deficits during maximal voluntary contractions at 30° and 180°/s (Kin-Com dynamometer). These work deficits were accompanied by proportional decreases in the prime mover or agonist-EMG levels (VM: vastus medialis and/or VL: vastus lateralis). These patients had smaller deficits during flexion movements at 30°/s. Moreover, a larger number of negative clinical signs and symptoms (pain at rest and during tests, locking, thigh atrophy, extension and flexion movement deficits larger than 10°) were found with an equal or a higher prevalence in group B than in the other groups. Patients with flap tears (group F, n=15) had deficits in work and agonist-EMG activity (VM and VL) only during the extension tests. In contrast, patients with degenerative tears (group D, n=8) had a work deficit and a concomitant decrease in the EMG level of the medial gastrocnemius (MG), only during the flexion test at 30°/s. Comparable mean knee function scores, as measured by the Lysholm and Gillquist questionnaire [35], were obtained for the three groups of patients, suggesting that this measure was not sensitive enough to discern functional differences related to types of meniscal tears. The results of this study have demonstrated a link between the type of meniscal lesion and the consequent preoperative knee joint disability profile as defined by comparison with the sound leg. These results emphasize the need to consider meniscal lesion type and an individual's preoperative strength deficit when group comparisons of patients are made or the effects of therapy (arthroscopic surgery and rehabilitation) are evaluated.