Fatty Acids Composition and HIV Infection: Altered Levels of n-6 Polyunsaturated Fatty Acids Are Associated with Disease Progression

Fatty acids (FAs) are important regulators of immune responses and innate defense mechanisms. We hypothesized that disturbed FA metabolism could contribute to the progression of HIV infection. Plasma levels of 45 FAs were analyzed with gas chromatography in healthy controls and HIV-infected patients with regard to Mycobacterium avium complex (MAC) infection. In vitro, we assessed MAC-PPD-induced release of inflammatory cytokines in peripheral and bone marrow mononuclear cells (PBMC and BMMC) according to levels of n-6 polyunsaturated fatty acids (PUFAs). While plasma saturated FAs were higher in HIV infection, PUFAs, and in particular the n-6 PUFA arachidonic acid (AA), were lower in patients with advanced disease. The ratio between AA and precursor dihomo-γ-linolenic acid, reflecting Δ5-desaturase activity, was markedly lower and inversely correlated with plasma HIV RNA levels in these patients. Depletion of AA was observed prior to MAC infection, and MAC-PPD-induced release of TNF and IL-6 in PBMC and BMMC was lower in patients with low plasma AA. Our findings suggest that dysregulated metabolism of n-6 PUFAs may play a role in the progression of HIV infection. While high AA may contribute to chronic inflammation in asymptomatic HIV-infected patients, low AA seems to increase the susceptibility to MAC infection in patients with advanced disease.publishedVersio

Kommunal avløpssektor : Gebyrer 2005 - utslipp, rensing og slamdisponering 2004

Denne rapporten presenterer status innen kommunal avløpssektor og rensing av avløpsvann fra den norske befolkning. Statistikken omtaler blant annet nivået på ressursinnsatsen, kommunale avløpsgebyrer samt utslipp av fosfor, nitrogen, organisk materiale, tungmetaller og organiske miljøgifter. I tillegg kartlegger rapporten renseeffekt, antall avløpsanlegg, kapasiteten ved anleggene, tilknytningsandelen til kommunalt ledningsnett, dessuten disponering og innhold av tungmetall i avløpsslam

Changes in 6-min walk test is an independent predictor of death in chronic heart failure with reduced ejection fraction

Aims Functional capacity provides important clinical information in patients with heart failure (HF) and reduced ejection fraction (HFrEF). The 6-min walk test (6MWT) is a simple and inexpensive tool for assessing functional capacity and risk. Although change in 6MWT is frequently used as a surrogate outcome in HF trials, the association with mortality is unclear. We aimed to assess the prognostic importance of changes in 6MWT. Methods and results Patients with chronic HFrEF referred to HF outpatient clinics in Norway completed a 6MWT at the first visit (baseline) and at a stable follow-up visit after treatment optimization (follow-up). Absolute and relative changes in 6MWT were analysed in association with mortality risk using Cox regression models and flexible cubic splines. The study included 3636 HFrEF patients aged 67.3 ± 11.6 years, 23% women, with left ventricular ejection fraction 30 ± 7%. At baseline, mean 6MWT was 438 ± 125 m, median N-terminal pro-B-type natriuretic peptide (NT-proBNP) 1574 (732–3093) ng/L, and 27% had New York Heart Association (NYHA) class III/IV. After optimization of guideline-directed medical therapy (median 147 [86–240] days), 6MWT increased by mean 40 ± 74 m, NT-proBNP decreased by median 425 (14–1322) ng/L, and NYHA class improved in 38% of patients. Patients with greater improvements in 6MWT were younger, with greater improvements in NYHA class (r = 0.27, p < 0.001) and larger reductions in NT-proBNP concentrations (r = 0.19, p < 0.001). After mean 845 ± 595 days, 419 (11.5%) patients were dead. Both absolute and relative changes in 6MWT were non-linearly associated with survival, attenuating as 6MWT increased. A 50 m increase in 6MWT was associated with a 17% lower mortality risk (hazard ratio 0.84, 95% confidence interval 0.77–0.90, p < 0.001) in the fully adjusted model, including changes in NYHA class, NT-proBNP concentrations, and other established risk factors. The associations were more pronounced in patients with lower baseline 6MWT and higher age. Conclusion Improvement in 6MWT in patients with HFrEF is associated with increased survival, independent of changes in NT-proBNP and NYHA class. These findings support 6MWT change as a surrogate outcome in HF trials.publishedVersio

Induction of mitochondrial biogenesis and respiration is associated with mTOR regulation in hepatocytes of rats treated with the pan-PPAR activator tetradecylthioacetic acid (TTA)

The hypolipidemic effect of peroxisome proliferator-activated receptor (PPAR) activators has been explained by increasing mitochondrial fatty acid oxidation, as observed in livers of rats treated with the pan-PPAR activator tetradecylthioacetic acid (TTA). PPAR-activation does, however, not fully explain the metabolic adaptations observed in hepatocytes after treatment with TTA. We therefore characterized the mitochondrial effects, and linked this to signalling by the metabolic sensor, the mammalian target of rapamycin (mTOR). In hepatocytes isolated from TTA-treated rats, the changes in cellular content and morphology were consistent with hypertrophy. This was associated with induction of multiple mitochondrial biomarkers, including mitochondrial DNA, citrate synthase and mRNAs of mitochondrial proteins. Transcription analysis further confirmed activation of PPARα-associated genes, in addition to genes related to mitochondrial biogenesis and function. Analysis of mitochondrial respiration revealed that the capacity of both electron transport and oxidative phosphorylation were increased. These effects coincided with activation of the stress related factor, ERK1/2, and mTOR. The protein level and phosphorylation of the downstream mTOR actors eIF4G and 4E-BP1 were induced. In summary, TTA increases mitochondrial respiration by inducing hypertrophy and mitochondrial biogenesis in rat hepatocytes, via adaptive regulation of PPARs as well as mTOR.acceptedVersio

Kommunale avløp : Ressursinnsats, utslipp, rensing og slamdisponering 2006, gebyrer 2007

Denne rapporten sammenfatter de viktigste resultatene knyttet til rensing av avløpsvann fra kommunal sektor. Statistikkene viser nivået på ressursinnsatsen (2006) og de kommunale avløpsgebyrene (2007). I tillegg omtales de viktigste trekkene ved avløpsbehandlingen i 2006, blant annet utslipp av fosfor og nitrogen, renseeffekt, antall avløpsanlegg, kapasitet, tilknytningsgrad, disponering av avløpsslam og innhold av tungmetall i slammet. Vannkvaliteten i Nordsjøen påvirkes av vannkvaliteten i vassdrag og kystfarvann i de landene som omkranser havområdet. For Norges del blir fylkene som drenerer til Nordsjøen gjerne omtalt som "Nordsjøfylkene" (se definisjon i kapittel 2). Norge har inngått flere avtaler (Nordsjø-deklarasjonene - den siste i Bergen i 2002) med de øvrige landene som har vassdrag med utløp til Nordsjøen. Avtalene omfatter en hel rekke påvirkningsfaktorer for Nordsjøen, deriblant påvirkning fra befolkningen i form av utslipp fra avløpsanlegg. Landene forpliktet seg gjennom avtalene til innen 2005 å redusere totale utslipp til Nordsjøområdet av næringsstoffene fosfor og nitrogen med 50 prosent, sammenlignet med 1985. Sett samlet for alle samfunnssektorer, inklusive utslipp fra kommunal avløpssektor, klarte Norge reduksjonsmålet for fosfor, men ikke for nitrogen. Reduksjonen var på 64 prosent for fosfor og 42 prosent for nitrogen (Selvik m.fl. 2006, s. 29

Kommunal avløpssektor : Gebyrer 2006 - utslipp, rensing og slamdisponering 2005

Denne rapporten sammenfatter de viktigste resultatene knyttet til rensing av avløpsvann fra kommunal sektor. Statistikkene viser nivået på de kommunale avløpsgebyrene i 2006 samt de viktigste trekkene ved avløpsbehandlingen i 2005, blant annet utslipp av fosfor og nitrogen, renseeffekt, antall avløpsanlegg, kapasitet, tilknytningsgrad, disponering og innhold av tungmetall i avløpsslam. Vannkvaliteten i Nordsjøen påvirkes av vannkvaliteten i vassdrag og kystfarvann i de landene som omkranser havområdet. For Norges del blir fylkene som drenerer til Nordsjøen gjerne omtalt som "Nordsjøfylkene" (se definisjon i kapittel 2). Norge har inngått flere avtaler (Nordsjø-deklarasjonene - den siste i Bergen i 2002) med de øvrige landene som har vassdrag med utløp til Nordsjøen. Avtalene omfatter en hel rekke påvirkningsfaktorer for Nordsjøen, deriblant påvirkning fra befolkningen i form av utslipp fra avløpsanlegg. Landene forpliktet seg gjennom avtalene til innen 2005 å redusere totale utslipp av næringsstoffene fosfor og nitrogen med 50 prosent, sammenlignet med 1985. Sett samlet for alle samfunnssektorer, inklusivt utslipp fra kommunalt avløpsvann, er Norges mål for lengst nådd for fosfor, mens det for nitrogen per 2004 fortsatt gjenstår en reduksjon på 10 prosent for å tilfredsstille kravene i Nordsjøavtalen. De fleste avløpsanlegg i Norge har sitt utslipp i kystfarvann eller vassdrag (resipienter). Den delen av næringsstoffene og annet utslipp som ikke fjernes ved renseanleggene transporteres via vassdragene og i siste instans ut i kystfarvann og havområder. Den stadige tilførselen av næringsstoffer til vassdrag og sjøvann kan medføre en overgjødsling (eutrofiering) av vannforekomstene, som igjen kan medføre uønsket høy algeproduksjon og forrykning av balansen i vannforekomstenes økosystemer

Plasma Cholesterol- and Body Fat-Lowering Effects of Chicken Protein Hydrolysate and Oil in High-Fat Fed Male Wistar Rats

Rest raw materials provide a new source of bioactive dietary ingredients, and this study aimed to determine the health effects of diets with chicken protein hydrolysate (CPH) and chicken oil (CO) generated from deboned chicken meat. Male Wistar rats (n = 56) were divided into seven groups in three predefined sub-experiments to study the effects of protein source (casein, chicken fillet, pork fillet, and CPH), the dose-effect of CPH (50% and 100% CPH), and the effects of combining CPH and CO. Rats were fed high-fat diets for 12 weeks, and casein and chicken fillet were used as controls in all sub-experiments. While casein, chicken-, or pork fillet diets resulted in similar weight gain and plasma lipid levels, the CPH diet reduced plasma total cholesterol. This effect was dose dependent and accompanied with the reduced hepatic activities of acetyl-CoA carboxylase and fatty acid synthase. Further, rats fed combined CPH and CO showed lower weight gain, and higher hepatic mitochondrial fatty acid oxidation, plasma L-carnitine, short-chain acylcarnitines, TMAO, and acetylcarnitine/palmitoylcarnitine. Thus, in male Wistar rats, CPH and CO lowered plasma cholesterol and increased hepatic fatty acid oxidation compared to whole protein diets, pointing to potential health-beneficial bioactive properties of these processed chicken rest raw materials.publishedVersio

Fish oil and krill oil supplementations differentially regulate lipid catabolic and synthetic pathways in mice

Background: Marine derived oils are rich in long-chain polyunsaturated omega-3 fatty acids, in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which have long been associated with health promoting effects such as reduced plasma lipid levels and anti-inflammatory effects. Krill oil (KO) is a novel marine oil on the market and is also rich in EPA and DHA, but the fatty acids are incorporated mainly into phospholipids (PLs) rather than triacylglycerols (TAG). This study compares the effects of fish oil (FO) and KO on gene regulation that influences plasma and liver lipids in a high fat diet mouse model. Methods: Male C57BL/6J mice were fed either a high-fat diet (HF) containing 24% (wt/wt) fat (21.3% lard and 2.3% soy oil), or the HF diet supplemented with FO (15.7% lard, 2.3% soy oil and 5.8% FO) or KO (15.6% lard, 2.3% soy oil and 5.7% KO) for 6 weeks. Total levels of cholesterol, TAG, PLs, and fatty acid composition were measured in plasma and liver. Gene regulation was investigated using quantitative PCR in liver and intestinal epithelium. Results: Plasma cholesterol (esterified and unesterified), TAG and PLs were significantly decreased with FO. Analysis of the plasma lipoprotein particles indicated that the lipid lowering effect by FO is at least in part due to decreased very low density lipoprotein (VLDL) content in plasma with subsequent liver lipid accumulation. KO lowered plasma non-esterified fatty acids (NEFA) with a minor effect on fatty acid accumulation in the liver. In spite of a lower omega-3 fatty acid content in the KO supplemented diet, plasma and liver PLs omega-3 levels were similar in the two groups, indicating a higher bioavailability of omega-3 fatty acids from KO. KO more efficiently decreased arachidonic acid and its elongation/desaturation products in plasma and liver. FO mainly increased the expression of several genes involved in fatty acid metabolism, while KO specifically decreased the expression of genes involved in the early steps of isoprenoid/ cholesterol and lipid synthesis. Conclusions: The data show that both FO and KO promote lowering of plasma lipids and regulate lipid homeostasis, but with different efficiency and partially via different mechanisms

Disturbed lipid profile in common variable immunodeficiency – a pathogenic loop of inflammation and metabolic disturbances

The relationship between metabolic and inflammatory pathways play a pathogenic role in various cardiometabolic disorders and is potentially also involved in the pathogenesis of other disorders such as cancer, autoimmunity and infectious diseases. Common variable immunodeficiency (CVID) is the most common primary immunodeficiency in adults, characterized by increased frequency of airway infections with capsulated bacteria. In addition, a large proportion of CVID patients have autoimmune and inflammatory complications associated with systemic inflammation. We summarize the evidence that support a role of a bidirectional pathogenic interaction between inflammation and metabolic disturbances in CVID. This include low levels and function of high-density lipoprotein (HDL), high levels of triglycerides (TG) and its major lipoprotein very low-density lipoprotein (VLDL), and an unfavorable fatty acid (FA) profile. The dysregulation of TG, VLDL and FA were linked to disturbed gut microbiota profile, and TG and VLDL levels were strongly associated with lipopolysaccharides (LPS), a marker of gut leakage in blood. Of note, the disturbed lipid profile in CVID did not include total cholesterol levels or high low-density lipoprotein levels. Furthermore, increased VLDL and TG levels in blood were not associated with diet, high body mass index and liver steatosis, suggesting a different phenotype than in patients with traditional cardiovascular risk such as metabolic syndrome. We hypothesize that these metabolic disturbances are linked to inflammation in a bidirectional manner with disturbed gut microbiota as a potential contributing factor.publishedVersio

One-Year Treatment with Olanzapine Depot in Female Rats: Metabolic Effects

Background Antipsychotic drugs can negatively affect the metabolic status of patients, with olanzapine as one of the most potent drugs. While patients are often medicated for long time periods, experiments in rats typically run for 1 to 12 weeks, showing olanzapine-related weight gain and increased plasma lipid levels, with transcriptional upregulation of lipogenic genes in liver and adipose tissue. It remains unknown whether metabolic status will deteriorate with time. Methods To examine long-term metabolic effects, we administered intramuscular long-acting injections of olanzapine (100 mg/kg BW) or control substance to female rats for up to 13 months. Results Exposure to olanzapine long-acting injections led to rapid weight gain, which was sustained throughout the experiment. At 1, 6, and 13 months, plasma lipid levels were measured in separate cohorts of rats, displaying no increase. Hepatic transcription of lipid-related genes was transiently upregulated at 1 month. Glucose and insulin tolerance tests indicated insulin resistance in olanzapine-treated rats after 12 months. Conclusion Our data show that the continuous increase in body weight in response to long-term olanzapine exposure was accompanied by surprisingly few concomitant changes in plasma lipids and lipogenic gene expression, suggesting that adaptive mechanisms are involved to reduce long-term metabolic adverse effects of this antipsychotic agent in rats.publishedVersio