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- Hyysalo, Jenni, et al.
(författare)
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Genetic variation in PNPLA3 but not APOC3 influences liver fat in non-alcoholic fatty liver disease
- 2012
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Ingår i: Journal of Gastroenterology and Hepatology. - : Wiley. - 0815-9319. ; 27:5, s. 951-956
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aim: A recent study in Indian subjects suggested common variants in apolipoprotein C3 (APOC3) (T-455C at rs2854116 and C-482T at rs2854117) to contribute to non-alcoholic fatty liver disease (NAFLD), plasma apoC3 and triglyceride concentrations. Our aim was to determine the contribution of genetic variation in APOC3 on liver fat content and plasma triglyceride and apoC3 concentrations in a larger European cohort. Methods: Atotal of 417 Finnish individuals were genotyped for rs2854116 and rs2854117 in APOC3 and the known rs738409 in patatin-like phospholipase domain-containing protein 3 (PNPLA3) influencing liver fat. Plasma apoC3 concentration was measured enzymatically, and liver fat by proton magnetic resonance spectroscopy. Results: APOC3 wild-type homozygotes and variant allele (T-455C or C-482T or both) carriers did not differ with regard to liver fat, apoC3 concentrations, triglyceride-, high density lipoprotein-, fasting plasma glucose, insulin-, alanine aminotransferase-and aspartate aminotransferase-concentrations, nor was there a difference in prevalence of NAFLD. In contrast, carriers of the PNPLA3 GG genotype at rs738409 had a 2.7-fold (median 11.3%) higher liver fat than those with the CC (median 4.2%) genotype. The PNPLA3 rs738409 was also an independent predictor of liver fat, together with age, gender, and body mass index. Conclusion: Genetic variants in PNPLA3 but not APOC3 contribute to the variance in liver fat content due to NAFLD.
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| 2. |
- Kolak, Maria, et al.
(författare)
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Adipose tissue inflammation and increased ceramide content characterize subjects with high liver fat content independent of obesity
- 2007
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 56:8, s. 1960-1968
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We sought to determine whether adipose tissue is inflamed in individuals with increased liver fat (LFAT) independently of obesity.RESEARCH DESIGN AND METHODS: A total of 20 nondiabetic, healthy, obese women were divided into normal and high LFAT groups based on their median LFAT level (2.3 +/- 0.3 vs. 14.4 +/- 2.9%). Surgical subcutaneous adipose tissue biopsies were studied using quantitative PCR, immunohistochemistry, and a lipidomics approach to search for putative mediators of insulin resistance and inflammation. The groups were matched for age and BMI. The high LFAT group had increased insulin (P = 0.0025) and lower HDL cholesterol (P = 0.02) concentrations.RESULTS: Expression levels of the macrophage marker CD68, the chemokines monocyte chemoattractant protein-1 and macrophage inflammatory protein-1alpha, and plasminogen activator inhibitor-1 were significantly increased, and those of peroxisome proliferator-activated receptor-gamma and adiponectin decreased in the high LFAT group. CD68 expression correlated with the number of macrophages and crown-like structures (multiple macrophages fused around dead adipocytes). Concentrations of 154 lipid species in adipose tissue revealed several differences between the groups, with the most striking being increased concentrations of triacylglycerols, particularly long chain, and ceramides, specifically Cer(d18:1/24:1) (P = 0.01), in the high LFAT group. Expression of sphingomyelinases SMPD1 and SMPD3 were also significantly increased in the high compared with normal LFAT group.CONCLUSIONS: Adipose tissue is infiltrated with macrophages, and its content of long-chain triacylglycerols and ceramides is increased in subjects with increased LFAT compared with equally obese subjects with normal LFAT content. Ceramides or their metabolites could contribute to adverse effects of long-chain fatty acids on insulin resistance and inflammation.
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| 3. |
- Mayer, Ludovic, et al.
(författare)
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Widespread Pesticide Distribution in the European Atmosphere Questions their Degradability in Air
- 2024
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Ingår i: Environmental Science and Technology. - 0013-936X. ; 58:7, s. 3342-3352
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Tidskriftsartikel (refereegranskat)abstract
- Risk assessment of pesticide impacts on remote ecosystems makes use of model-estimated degradation in air. Recent studies suggest these degradation rates to be overestimated, questioning current pesticide regulation. Here, we investigated the concentrations of 76 pesticides in Europe at 29 rural, coastal, mountain, and polar sites during the agricultural application season. Overall, 58 pesticides were observed in the European atmosphere. Low spatial variation of 7 pesticides suggests continental-scale atmospheric dispersal. Based on concentrations in free tropospheric air and at Arctic sites, 22 pesticides were identified to be prone to long-range atmospheric transport, which included 15 substances approved for agricultural use in Europe and 7 banned ones. Comparison between concentrations at remote sites and those found at pesticide source areas suggests long atmospheric lifetimes of atrazine, cyprodinil, spiroxamine, tebuconazole, terbuthylazine, and thiacloprid. In general, our findings suggest that atmospheric transport and persistence of pesticides have been underestimated and that their risk assessment needs to be improved.
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