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- Kotronen, A., et al.
(författare)
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Serum saturated fatty acids containing triacylglycerols are better markers of insulin resistance than total serum triacylglycerol concentrations
- 2009
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Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 52:4, s. 684-690
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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.
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| 2. |
- Kotronen, A., et al.
(författare)
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A common variant in PNPLA3, which encodes adiponutrin, is associated with liver fat content in humans
- 2009
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 52:6, s. 1056-1060
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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.
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| 5. |
- Bergholm, U, et al.
(författare)
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Long term follow-up of patients with medullary carcinoma of the thyroid
- 1997
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Ingår i: CANCER. - : WILEY-LISS. - 0008-543X. ; 79:1, s. 132-138
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. All patients with medullary carcinoma of the thyroid (MCT) diagnosed in Sweden during 1959 through 1981 were identified. There were 113 males and 134 females with a mean age of 51.6 years (range, 11-85 years). The cohort was followed with rega
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| 6. |
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| 7. |
- 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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| 9. |
- Sysi-Aho, Marko, et al.
(författare)
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Exploring the lipoprotein composition using Bayesian regression on serum lipidomic profiles
- 2007
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Ingår i: Bioinformatics. - : Oxford University Press. - 1367-4803 .- 1367-4811 .- 1460-2059. ; 23:13, s. i519-i528
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Tidskriftsartikel (refereegranskat)abstract
- MOTIVATION: Serum lipids have been traditionally studied in the context of lipoprotein particles. Today's emerging lipidomics technologies afford sensitive detection of individual lipid molecular species, i.e. to a much greater detail than the scale of lipoproteins. However, such global serum lipidomic profiles do not inherently contain any information on where the detected lipid species are coming from. Since it is too laborious and time consuming to routinely perform serum fractionation and lipidomics analysis on each lipoprotein fraction separately, this presents a challenge for the interpretation of lipidomic profile data. An exciting and medically important new bioinformatics challenge today is therefore how to build on extensive knowledge of lipid metabolism at lipoprotein levels in order to develop better models and bioinformatics tools based on high-dimensional lipidomic data becoming available today.RESULTS: We developed a hierarchical Bayesian regression model to study lipidomic profiles in serum and in different lipoprotein classes. As a background data for the model building, we utilized lipidomic data for each of the lipoprotein fractions from 5 subjects with metabolic syndrome and 12 healthy controls. We clustered the lipid profiles and applied a regression model within each cluster separately. We found that the amount of a lipid in serum can be adequately described by the amounts of lipids in the lipoprotein classes. In addition to improved ability to interpret lipidomic data, we expect that our approach will also facilitate dynamic modelling of lipid metabolism at the individual molecular species level.
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