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- Naukkarinen, J., et al.
(författare)
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Characterising metabolically healthy obesity in weight-discordant monozygotic twins
- 2014
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Ingår i: Diabetologia. - New York, USA : Springer. - 0012-186X .- 1432-0428. ; 57:1, s. 167-176
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: Not all obese individuals display the metabolic disturbances commonly associated with excess fat accumulation. Mechanisms maintaining this ‘metabolically healthy obesity’ (MHO) are as yet unknown. We aimed to study different fat depots and transcriptional pathways in subcutaneous adipose tissue (SAT) as related to the MHO phenomenon.Methods: Sixteen rare young adult obesity-discordant monozygotic (MZ) twin pairs (intra-pair difference (∆) in BMI ≥3 kg/m2), aged 22.8–35.8 years, were examined for detailed characteristics of metabolic health (subcutaneous, intra-abdominal and liver fat [magnetic resonance imaging/spectroscopy]), OGTT, lipids, adipokines and C-reactive protein (CRP). Affymetrix U133 Plus 2.0 chips were used to analyse transcriptomics pathways related to mitochondrial function and inflammation in SAT.Results: Based on liver fat accumulation, two metabolically different subgroups emerged. In half (8/16) of the pairs (∆weight 17.1 ± 2.0 kg), the obese co-twin had significantly higher liver fat (∆718%), 78% increase in AUC insulin during OGTT and CRP, significantly more disturbance in the lipid profile and greater tendency for hypertension compared with the lean co-twin. In these obese co-twins, SAT expression of mitochondrial oxidative phosphorylation, branched-chain amino acid catabolism, fatty acid oxidation and adipocyte differentiation pathways were downregulated and chronic inflammation upregulated. In the other eight pairs (∆weight 17.4 ± 2.8 kg), the obese co-twin did not differ from the non-obese co-twin in liver fat (∆8%), insulin sensitivity, CRP, lipids, blood pressure or SAT transcriptomics.Conclusions/interpretation: Our results suggest that maintenance of high mitochondrial transcription and lack of inflammation in SAT are associated with low liver fat and MHO.
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- Harvima, IT, et al.
(författare)
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Is there a role for mast cells in psoriasis?
- 2008
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Ingår i: Archives of dermatological research. - : Springer Science and Business Media LLC. - 1432-069X .- 0340-3696. ; 300:9, s. 461-478
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Tidskriftsartikel (refereegranskat)
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- Harvima, IT, et al.
(författare)
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Role of mast cells and sensory nerves in skin inflammation
- 2010
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Ingår i: Giornale italiano di dermatologia e venereologia : organo ufficiale, Societa italiana di dermatologia e sifilografia. - 0392-0488. ; 145:2, s. 195-204
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Tidskriftsartikel (refereegranskat)
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- Naukkarinen, Jussi, et al.
(författare)
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Functional Variant Disrupts Insulin Induction of USF1 Mechanism for USF1-Associated Dyslipidemias
- 2009
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Ingår i: Circulation: Cardiovascular Genetics. - 1942-325X. ; 2:5, s. 245-522
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Tidskriftsartikel (refereegranskat)abstract
- Background-The upstream transcription factor 1 (USF1) gene is associated with familial combined hyperlipidemia, the most common genetic dyslipidemia in humans, as well as with various dyslipidemic changes in numerous other studies. Typical of complex disease-associated genes, neither the explicit mutations have been described nor the functional consequences for risk allele carriers been reported at the cellular or tissue level. Methods and Results-In this study, we aimed at describing the molecular mechanism through which the strongest associating intronic single-nucleotide polymorphism variant in USF1 is involved in the development of dyslipidemia. The effects of the risk variant on gene expression were studied in 2 relevant human tissues, fat and muscle. Global transcript profiles of 47 fat biopsies ascertained for carriership of the risk allele were tested for differential expression of known USF1 target genes as well as for broader effects on the transcript profile. Allelic imbalance of USF1 in fat was assessed using a quantitative sequencing approach. The possible allele-specific effect of insulin on the expression of USF1 was studied in 118 muscle biopsies before and after a euglycemic hyperinsulinemic clamp. The risk allele of single-nucleotide polymorphism rs2073658 seems to eradicate the inductive effect of insulin on the expression of USF1 in muscle and fat. The expression of numerous target genes is in turn perturbed in adipose tissue. Conclusions-In risk allele carriers, a defective response of USF1 to insulin results in the suboptimal response of relevant target genes that contributes to the enhanced risk of developing dyslipidemia and coronary heart disease. (Circ Cardiovasc Genet. 2009;2:522-529.)
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