| 1. |
|
|
| 2. |
|
|
| 3. |
- Kotronen, A., et al.
(författare)
-
A common variant in PNPLA3, which encodes adiponutrin, is associated with liver fat content in humans
- 2009
-
Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 52:6, s. 1056-1060
-
Tidskriftsartikel (refereegranskat)abstract
- It has recently been suggested that the rs738409 G allele in PNPLA3, which encodes adiponutrin, is strongly associated with increased liver fat content in three different ethnic groups. The aims of the present study were as follows: (1) to try to replicate these findings in European individuals with quantitative measures of hepatic fat content; (2) to study whether the polymorphism influences hepatic and adipose tissue insulin sensitivity; and (3) to investigate whether PNPLA3 expression is altered in the human fatty liver. We genotyped 291 Finnish individuals in whom liver fat had been measured using proton magnetic resonance spectroscopy. Hepatic PNPLA3 expression was measured in 32 participants. Hepatic and adipose tissue insulin sensitivities were measured using a euglycaemic-hyperinsulinaemic (insulin infusion 0.3 mU kg(-1) min(-1)) clamp technique combined with infusion of [3-H-3]glucose in 109 participants. The rs738409 G allele in PNPLA3 was associated with increased quantitative measures of liver fat content (p = 0.011) and serum aspartate aminotransferase concentrations (p = 0.002) independently of age, sex and BMI. Fasting serum insulin and hepatic and adipose tissue insulin sensitivity were related to liver fat content independently of genotype status. PNPLA3 mRNA expression in the liver was positively related to obesity (r = 0.62, p < 0.0001) and to liver fat content (r = 0.58, p = 0.025) in participants who were not morbidly obese (BMI < 40 kg/m(2)). A common variant in PNPLA3 increases the risk of hepatic steatosis in humans.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Herling, L., et al.
(författare)
-
Automated analysis of fetal cardiac function using color tissue Doppler imaging
- 2018
-
Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 52:5, s. 599-608
-
Tidskriftsartikel (refereegranskat)abstract
- Objective To evaluate the feasibility of automated analysis of fetal myocardial velocity recordings obtained by color tissue Doppler imaging (cTDI). Methods This was a prospective cross-sectional observational study of 107 singleton pregnancies >= 41 weeks of gestation. Myocardial velocity recordings were obtained by cTDI in a long-axis four-chamber view of the fetal heart. Regions of interest were placed in the septum and the right (RV) and left (LV) ventricular walls at the level of the atrioventricular plane. Peak myocardial velocities and mechanical cardiac time intervals were measured both manually and by an automated algorithm and agreement between the two methods was evaluated. Results In total, 321 myocardial velocity traces were analyzed using each method. It was possible to analyze all velocity traces obtained from the LV, RV and septal walls with the automated algorithm, and myocardial velocities and cardiac mechanical time intervals could be measured in 96% of all traces. The same results were obtained when the algorithm was run repeatedly. The myocardial velocities measured using the automated method correlated significantly with those measured manually. The agreement between methods was not consistent and some cTDI parameters had considerable bias and poor precision. Conclusions Automated analysis of myocardial velocity recordings obtained by cTDI was feasible, suggesting that this technique could simplify and facilitate the use of cTDI in the evaluation of fetal cardiac function, both in research and in clinical practice.
|
|
| 7. |
- Herling, L., et al.
(författare)
-
Automated analysis of fetal cardiac function using color tissue Doppler imaging in second half of normal pregnancy
- 2019
-
Ingår i: Ultrasound in Obstetrics and Gynecology. - : WILEY. - 0960-7692 .- 1469-0705. ; 53:3, s. 348-357
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives Color tissue Doppler imaging (cTDI) is a promising tool for the assessment of fetal cardiac function. However, the analysis of myocardial velocity traces is cumbersome and time-consuming, limiting its application in clinical practice. The aim of this study was to evaluate fetal cardiac function during the second half of pregnancy and to develop reference ranges using an automated method to analyze cTDI recordings from a cardiac four-chamber view. Methods This was a cross-sectional study including 201 normal singleton pregnancies between 18 and 42weeks of gestation. During fetal echocardiography, a four-chamber view of the heart was visualized and cTDI was performed. Regions of interest were positioned at the level of the atrioventricular plane in the left ventricular (LV), right ventricular (RV) and septal walls of the fetal heart, to obtain myocardial velocity traces that were analyzed offline using the automated algorithm. Peak myocardial velocities during atrial contraction (Am), ventricular ejection (Sm) and rapid ventricular filling, i. e. early diastole (Em), as well as the Em/Am ratio, mechanical cardiac time intervals and myocardial performance index (cMPI) were evaluated, and gestational age-specific reference ranges were constructed. Results At 18 weeks of gestation, the peak myocardial velocities, presented as fitted mean with 95% CI, were: LV Am, 3.39 (3.09-3.70) cm/s; LV Sm, 1.62 (1.46-1.79) cm/s; LV Em, 1.95 (1.75-2.15) cm/s; septal Am, 3.07 (2.80-3.36) cm/s; septal Sm, 1.93 (1.81-2.06) cm/s; septal Em, 2.57 (2.32-2.84) cm/s; RV Am, 4.89 (4.59-5.20) cm/s; RV Sm, 2.31 (2.16-2.46) cm/s; and RV Em, 2.94 (2.69-3.21) cm/s. At 42weeks of gestation, the peak myocardial velocities had increased to: LV Am, 4.25 (3.87-4.65) cm/s; LV Sm, 3.53 (3.19-3.89) cm/s; LV Em, 4.55 (4.18-4.94) cm/s; septal Am, 4.49 (4.17-4.82) cm/s; septal Sm, 3.36 (3.17-3.55) cm/s; septal Em, 3.76 (3.51-4.03) cm/s; RV Am, 6.52 (6.09-6.96) cm/s; RV Sm, 4.95 (4.59-5.32) cm/s; and RV Em, 5.42 (4.99-5.88) cm/s. The mechanical cardiac time intervals generally remained more stable throughout the second half of pregnancy, although, with increased gestational age, there was an increase in duration of septal and RV atrial contraction, LV pre-ejection and septal and RV ventricular ejection, while there was a decrease in duration of septal postejection. Regression equations used for the construction of gestational age-specific reference ranges for peak myocardial velocities, Em/Am ratios, mechanical cardiac time intervals and cMPI are presented. Conclusion Peak myocardial velocities increase with gestational age, while the mechanical time intervals remain more stable throughout the second half of pregnancy. Using an automated method to analyze cTDI-derived myocardial velocity traces, it was possible to construct reference ranges, which could be used in distinguishing between normal and abnormal fetal cardiac function.
|
|
| 8. |
- Kolak, Maria, et al.
(författare)
-
Adipose tissue inflammation and increased ceramide content characterize subjects with high liver fat content independent of obesity
- 2007
-
Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 56:8, s. 1960-1968
-
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.
|
|
| 9. |
- Kotronen, Anna, et al.
(författare)
-
Genetic variation in the ADIPOR2 gene is associated with liver fat content and its surrogate markers in three independent cohorts
- 2009
-
Ingår i: European Journal of Endocrinology. - 1479-683X. ; 160:4, s. 593-602
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: We investigated whether polymorph isms in candidate genes involved in lipid metabolism and type 2 diabetes are related to liver I, at content. Methods: Liver fat content was measured using proton magnetic resonance spectroscopy (H-1-MRS) in 302 Finns, in whom single nucleotide polymorphisms (SNPs) in acyl-CoA synthetase long-chain family member 4 (ACSL4). acliponectin receptors 1 and 2 (ADIPOR1 and ADIPOR2), and the three peroxisome proliferator-activated receptors (PPARA, PPARD, and PPARG) were analyzed. To validate our findings, SNPs significantly associated with liver fat content were Studied in two independent cohorts and related to surrogate markers of liver fat content. Results: In the Finnish subjects, polymorphisms in ACSL4 (rs7887981), ADIPOR2 (rs767870), and PPARG (rs3856806) were significantly associated with liver fat content measured with H-1-MRS after adjusting for age, gender, and BMI, Anthropometric and circulating parameters were comparable between genotypes. In the first validation cohort of similar to 600 Swedish men, ACSL4 rs7887981 was related to fasting insulin and triglyceride concentrations, and ADIPOR2 rs767870 to serum gamma glutamyltransfer concentrations after adjusting for BMI. The SNP in PPARG (rs3856806) was not significantly associated with any relevant metabolic parameter in this cohort. In the second validation cohort of similar to 3000 subjects from Western Finland, ADIPOR2 rs767870, but not ACSL4 rs7887981 was related to fasting triglyceride concentrations. Conclusions: Genetic variation, particularly in the ADIPOR2 gene, contributes to variation in hepatic fat accumulation in humans.
|
|
| 10. |
- Kotronen, A., et al.
(författare)
-
Serum saturated fatty acids containing triacylglycerols are better markers of insulin resistance than total serum triacylglycerol concentrations
- 2009
-
Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 52:4, s. 684-690
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: The weak relationship between insulin resistance and total serum triacylglycerols (TGs) could be in part due to heterogeneity of TG molecules and their distribution within different lipoproteins. We determined concentrations of individual TGs and the fatty acid composition of serum and major lipoprotein particles and analysed how changes in different TGs and fatty acid composition are related to features of insulin resistance and abdominal obesity.METHODS: We performed lipidomic analyses of all major lipoprotein fractions using two analytical platforms in 16 individuals, who exhibited a broad range of insulin sensitivity.RESULTS: We identified 45 different TGs in serum. Serum TGs containing saturated and monounsaturated fatty acids were positively, while TGs containing essential linoleic acid (18:2 n-6) were negatively correlated with HOMA-IR. Specific serum TGs that correlated positively with HOMA-IR were also significantly positively related to HOMA-IR when measured in very-low-density lipoproteins (VLDLs), intermediate-density lipoproteins (IDLs) and LDL, but not in HDL subfraction 2 (HDL(2)) or 3 (HDL(3)). Analyses of proportions of esterified fatty acids within lipoproteins revealed that palmitic acid (16:0) was positively related to HOMA-IR when measured in VLDL, IDL and LDL, but not in HDL(2) or HDL(3). Monounsaturated palmitoleic (16:1 n-7) and oleic (18:1 n-9) acids were positively related to HOMA-IR when measured in HDL(2) and HDL(3), but not in VLDL, IDL or LDL. Linoleic acid was negatively related to HOMA-IR in all lipoproteins.CONCLUSIONS/INTERPRETATION: Serum concentrations of specific TGs, such as TG(16:0/16:0/18:1) or TG(16:0/18:1/18:0), may be more precise markers of insulin resistance than total serum TG concentrations.
|
|
